{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T06:48:01Z","timestamp":1792651681188,"version":"4.5.0"},"reference-count":147,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2020,2,1]],"date-time":"2020-02-01T00:00:00Z","timestamp":1580515200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2020,2,1]],"date-time":"2020-02-01T00:00:00Z","timestamp":1580515200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Genet"],"published-print":{"date-parts":[[2020,2]]},"DOI":"10.1038\/s41588-019-0575-8","type":"journal-article","created":{"date-parts":[[2020,2,14]],"date-time":"2020-02-14T12:02:42Z","timestamp":1581681762000},"page":"146-159","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":151,"title":["A slipped-CAG DNA-binding small molecule induces trinucleotide-repeat contractions in vivo"],"prefix":"10.1038","volume":"52","author":[{"given":"Masayuki","family":"Nakamori","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5750-6051","authenticated-orcid":false,"given":"Gagan B.","family":"Panigrahi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stella","family":"Lanni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terence","family":"Gall-Duncan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideki","family":"Hayakawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hana","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Otabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinxing","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiro","family":"Sakata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Christine","family":"Caron","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niraj","family":"Joshi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanya","family":"Prasolava","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Chiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Yves","family":"Masson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc S.","family":"Wold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9913-680X","authenticated-orcid":false,"given":"Xiaoxiao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8696-6962","authenticated-orcid":false,"given":"Marietta Y. W. T.","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Huddleston","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8413-6498","authenticated-orcid":false,"given":"Katherine M.","family":"Munson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"Davidson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehdi","family":"Layeghifard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa-Monique","family":"Edward","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Gallon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauro","family":"Santibanez-Koref","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asako","family":"Murata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5513-5012","authenticated-orcid":false,"given":"Masanori P.","family":"Takahashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8246-4014","authenticated-orcid":false,"given":"Evan E.","family":"Eichler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Shlien","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1705-5265","authenticated-orcid":false,"given":"Kazuhiko","family":"Nakatani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0874-7542","authenticated-orcid":false,"given":"Hideki","family":"Mochizuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9545-4205","authenticated-orcid":false,"given":"Christopher E.","family":"Pearson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,2,14]]},"reference":[{"key":"575_CR1","doi-asserted-by":"publisher","first-page":"3359","DOI":"10.1093\/hmg\/ddg352","volume":"12","author":"L Kennedy","year":"2003","unstructured":"Kennedy, L. et al. Dramatic tissue-specific mutation length increases are an early molecular event in Huntington disease pathogenesis. Hum. Mol. Genet. 12, 3359\u20133367 (2003).","journal-title":"Hum. Mol. Genet."},{"key":"575_CR2","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1038\/nrm2854","volume":"11","author":"A Lopez Castel","year":"2010","unstructured":"Lopez Castel, A., Cleary, J. D. & Pearson, C. E. Repeat instability as the basis for human diseases and as a potential target for therapy. Nat. Rev. Mol. Cell Biol. 11, 165\u2013170 (2010).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"575_CR3","doi-asserted-by":"publisher","first-page":"932","DOI":"10.1038\/nature05977","volume":"447","author":"SM Mirkin","year":"2007","unstructured":"Mirkin, S. M. Expandable DNA repeats and human disease. Nature 447, 932\u2013940 (2007).","journal-title":"Nature"},{"key":"575_CR4","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1038\/nrg1689","volume":"6","author":"CE Pearson","year":"2005","unstructured":"Pearson, C. E., Nichol Edamura, K. & Cleary, J. D. Repeat instability: mechanisms of dynamic mutations. Nat. Rev. Genet. 6, 729\u2013742 (2005).","journal-title":"Nat. Rev. Genet."},{"key":"575_CR5","doi-asserted-by":"publisher","first-page":"692","DOI":"10.1007\/s004390050432","volume":"99","author":"K Sathasivam","year":"1997","unstructured":"Sathasivam, K., Amaechi, I., Mangiarini, L. & Bates, G. Identification of an HD patient with a (CAG)180 repeat expansion and the propagation of highly expanded CAG repeats in lambda phage. Hum. Genet. 99, 692\u2013695 (1997).","journal-title":"Hum. Genet."},{"key":"575_CR6","doi-asserted-by":"publisher","first-page":"3558","DOI":"10.1093\/hmg\/dds185","volume":"21","author":"F Morales","year":"2012","unstructured":"Morales, F. et al. Somatic instability of the expanded CTG triplet repeat in myotonic dystrophy type 1 is a heritable quantitative trait and modifier of disease severity. Hum. Mol. Genet. 21, 3558\u20133567 (2012).","journal-title":"Hum. Mol. Genet."},{"key":"575_CR7","doi-asserted-by":"publisher","first-page":"3039","DOI":"10.1093\/hmg\/ddp242","volume":"18","author":"M Swami","year":"2009","unstructured":"Swami, M. et al. Somatic expansion of the Huntington\u2019s disease CAG repeat in the brain is associated with an earlier age of disease onset. Hum. Mol. Genet. 18, 3039\u20133047 (2009).","journal-title":"Hum. Mol. Genet."},{"key":"575_CR8","doi-asserted-by":"publisher","first-page":"983","DOI":"10.1002\/ana.24656","volume":"79","author":"C Bettencourt","year":"2016","unstructured":"Bettencourt, C. et al. DNA repair pathways underlie a common genetic mechanism modulating onset in polyglutamine diseases. Ann. Neurol. 79, 983\u2013990 (2016).","journal-title":"Ann. Neurol."},{"key":"575_CR9","doi-asserted-by":"publisher","first-page":"516","DOI":"10.1016\/j.cell.2015.07.003","volume":"162","author":"Genetic Modifiers of Huntington\u2019s Disease Consortium","year":"2015","unstructured":"Genetic Modifiers of Huntington\u2019s Disease Consortium Identification of genetic factors that modify clinical onset of Huntington\u2019s disease. Cell 162, 516\u2013526 (2015).","journal-title":"Cell"},{"key":"575_CR10","unstructured":"Genetic Modifiers of Huntington\u2019s Disease (GeM-HD) Consortium. CAG repeat not polyglutamine length determines timing of Huntington\u2019s disease onset. Cell 178, 887\u2013900.e14 (2019)."},{"key":"575_CR11","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1016\/S1474-4422(17)30161-8","volume":"16","author":"DJ Hensman Moss","year":"2017","unstructured":"Hensman Moss, D. J. et al. Identification of genetic variants associated with Huntington\u2019s disease progression: a genome-wide association study. Lancet Neurol. 16, 701\u2013711 (2017).","journal-title":"Lancet Neurol."},{"key":"575_CR12","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1038\/35039051","volume":"1","author":"JF Gusella","year":"2000","unstructured":"Gusella, J. F. & MacDonald, M. E. Molecular genetics: unmasking polyglutamine triggers in neurodegenerative disease. Nat. Rev. Neurosci. 1, 109\u2013115 (2000).","journal-title":"Nat. Rev. Neurosci."},{"key":"575_CR13","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1002\/mds.24024","volume":"27","author":"A Rosenblatt","year":"2012","unstructured":"Rosenblatt, A. et al. Age, CAG repeat length, and clinical progression in Huntington\u2019s disease. Mov. Disord. 27, 272\u2013276 (2012).","journal-title":"Mov. Disord."},{"key":"575_CR14","doi-asserted-by":"publisher","first-page":"e1003866","DOI":"10.1371\/journal.pgen.1003866","volume":"9","author":"MM Axford","year":"2013","unstructured":"Axford, M. M. et al. Detection of slipped-DNAs at the trinucleotide repeats of the myotonic dystrophy type I disease locus in patient tissues. PLoS Genet. 9, e1003866 (2013).","journal-title":"PLoS Genet."},{"key":"575_CR15","doi-asserted-by":"publisher","first-page":"e1000749","DOI":"10.1371\/journal.pgen.1000749","volume":"5","author":"AV Goula","year":"2009","unstructured":"Goula, A. V. et al. Stoichiometry of base excision repair proteins correlates with increased somatic CAG instability in striatum over cerebellum in Huntington\u2019s disease transgenic mice. PLoS Genet. 5, e1000749 (2009).","journal-title":"PLoS Genet."},{"key":"575_CR16","doi-asserted-by":"publisher","first-page":"692","DOI":"10.1073\/pnas.0909740107","volume":"107","author":"Y Lin","year":"2010","unstructured":"Lin, Y., Dent, S. Y., Wilson, J. H., Wells, R. D. & Napierala, M. R loops stimulate genetic instability of CTG\u00b7CAG repeats. Proc. Natl Acad. Sci. USA 107, 692\u2013697 (2010).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"575_CR17","doi-asserted-by":"publisher","first-page":"4534","DOI":"10.1093\/nar\/gkf572","volume":"30","author":"CE Pearson","year":"2002","unstructured":"Pearson, C. E. et al. Slipped-strand DNAs formed by long (CAG)\u00b7(CTG) repeats: slipped-out repeats and slip-out junctions. Nucleic Acids Res. 30, 4534\u20134547 (2002).","journal-title":"Nucleic Acids Res."},{"key":"575_CR18","doi-asserted-by":"publisher","first-page":"10473","DOI":"10.1093\/nar\/gku658","volume":"42","author":"K Reddy","year":"2014","unstructured":"Reddy, K. et al. Processing of double-R-loops in (CAG)\u00b7(CTG) and C9orf72 (GGGGCC)\u00b7(GGCCCC) repeats causes instability. Nucleic Acids Res. 42, 10473\u201310487 (2014).","journal-title":"Nucleic Acids Res."},{"key":"575_CR19","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1016\/j.dnarep.2015.11.008","volume":"38","author":"MH Schmidt","year":"2016","unstructured":"Schmidt, M. H. & Pearson, C. E. Disease-associated repeat instability and mismatch repair. DNA Repair 38, 117\u2013126 (2016).","journal-title":"DNA Repair"},{"key":"575_CR20","doi-asserted-by":"publisher","first-page":"e1003280","DOI":"10.1371\/journal.pgen.1003280","volume":"9","author":"S Tome","year":"2013","unstructured":"Tome, S. et al. Msh3 polymorphisms and protein levels affect CAG repeat instability in Huntington\u2019s disease mice. PLoS Genet. 9, e1003280 (2013).","journal-title":"PLoS Genet."},{"key":"575_CR21","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1093\/hmg\/ddq501","volume":"20","author":"M Nakamori","year":"2011","unstructured":"Nakamori, M., Pearson, C. E. & Thornton, C. A. Bidirectional transcription stimulates expansion and contraction of expanded (CTG)\u00b7(CAG) repeats. Hum. Mol. Genet. 20, 580\u2013588 (2011).","journal-title":"Hum. Mol. Genet."},{"key":"575_CR22","doi-asserted-by":"publisher","first-page":"e46807","DOI":"10.1371\/journal.pone.0046807","volume":"7","author":"Y Lin","year":"2012","unstructured":"Lin, Y. & Wilson, J. H. Nucleotide excision repair, mismatch repair, and R-loops modulate convergent transcription-induced cell death and repeat instability. PLoS ONE 7, e46807 (2012).","journal-title":"PLoS ONE"},{"key":"575_CR23","doi-asserted-by":"publisher","first-page":"12593","DOI":"10.1073\/pnas.0909087107","volume":"107","author":"GB Panigrahi","year":"2010","unstructured":"Panigrahi, G. B., Slean, M. M., Simard, J. P., Gileadi, O. & Pearson, C. E. Isolated short CTG\/CAG DNA slip-outs are repaired efficiently by hMutS\u03b2, but clustered slip-outs are poorly repaired. Proc. Natl Acad. Sci. USA 107, 12593\u201312598 (2010).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"575_CR24","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1093\/nass\/nrl073","volume":"50","author":"M Hagihara","year":"2006","unstructured":"Hagihara, M. & Nakatani, K. Inhibition of DNA replication by a d(CAG) repeat binding ligand. Nucleic Acids Symp. Ser. 50, 147\u2013148 (2006).","journal-title":"Nucleic Acids Symp. Ser."},{"key":"575_CR25","doi-asserted-by":"publisher","first-page":"1686","DOI":"10.1002\/cbic.201100260","volume":"12","author":"M Hagihara","year":"2011","unstructured":"Hagihara, M., He, H. & Nakatani, K. Small molecule modulates hairpin structures in CAG trinucleotide repeats. ChemBioChem 12, 1686\u20131689 (2011).","journal-title":"ChemBioChem"},{"key":"575_CR26","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1038\/nchembio708","volume":"1","author":"K Nakatani","year":"2005","unstructured":"Nakatani, K. et al. Small-molecule ligand induces nucleotide flipping in (CAG)n trinucleotide repeats. Nat. Chem. Biol. 1, 39\u201343 (2005).","journal-title":"Nat. Chem. Biol."},{"key":"575_CR27","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1021\/bi00401a012","volume":"27","author":"PE Nielsen","year":"1988","unstructured":"Nielsen, P. E., Zhen, W. P., Henriksen, U. & Buchardt, O. Sequence-influenced interactions of oligoacridines with DNA detected by retarded gel electrophoretic migrations. Biochemistry 27, 67\u201373 (1988).","journal-title":"Biochemistry"},{"key":"575_CR28","doi-asserted-by":"publisher","first-page":"12277","DOI":"10.1073\/pnas.1311325110","volume":"110","author":"A Pluciennik","year":"2013","unstructured":"Pluciennik, A. et al. Extrahelical (CAG)\/(CTG) triplet repeat elements support proliferating cell nuclear antigen loading and MutL\u03b1 endonuclease activation. Proc. Natl Acad. Sci. USA 110, 12277\u201312282 (2013).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"575_CR29","doi-asserted-by":"publisher","first-page":"1133","DOI":"10.1093\/hmg\/ddm054","volume":"16","author":"PF Shelbourne","year":"2007","unstructured":"Shelbourne, P. F. et al. Triplet repeat mutation length gains correlate with cell-type specific vulnerability in Huntington disease brain. Hum. Mol. Genet. 16, 1133\u20131142 (2007).","journal-title":"Hum. Mol. Genet."},{"key":"575_CR30","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1001\/archneur.59.4.623","volume":"59","author":"I Silveira","year":"2002","unstructured":"Silveira, I. et al. Trinucleotide repeats in 202 families with ataxia: a small expanded (CAG)n allele at the SCA17 locus. Arch. Neurol. 59, 623\u2013629 (2002).","journal-title":"Arch. Neurol."},{"key":"575_CR31","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.dnarep.2016.10.003","volume":"49","author":"M Sanchez-Contreras","year":"2017","unstructured":"Sanchez-Contreras, M. & Cardozo-Pelaez, F. Age-related length variability of polymorphic CAG repeats. DNA Repair 49, 26\u201332 (2017).","journal-title":"DNA Repair"},{"key":"575_CR32","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1038\/sj.ejhg.5201954","volume":"16","author":"R Gao","year":"2008","unstructured":"Gao, R. et al. Instability of expanded CAG\/CAA repeats in spinocerebellar ataxia type 17. Eur. J. Hum. Genet. 16, 215\u2013222 (2008).","journal-title":"Eur. J. Hum. Genet."},{"key":"575_CR33","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1002\/humu.23721","volume":"40","author":"R Gallon","year":"2019","unstructured":"Gallon, R. et al. A sensitive and scalable microsatellite instability assay to diagnose constitutional mismatch repair deficiency by sequencing of peripheral blood leukocytes. Hum. Mutat. 40, 649\u2013655 (2019).","journal-title":"Hum. Mutat."},{"key":"575_CR34","first-page":"161","volume":"291","author":"P Keohavong","year":"2005","unstructured":"Keohavong, P., Xi, L. & Grant, S. G. Molecular analysis of mutations in the human HPRT gene. Methods Mol. Biol. 291, 161\u2013170 (2005).","journal-title":"Methods Mol. Biol."},{"key":"575_CR35","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1007\/978-1-62703-739-6_23","volume":"1105","author":"P Keohavong","year":"2014","unstructured":"Keohavong, P., Xi, L. & Grant, S. G. Molecular analysis of mutations in the human HPRT gene. Methods Mol. Biol. 1105, 291\u2013301 (2014).","journal-title":"Methods Mol. Biol."},{"key":"575_CR36","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1002\/em.21955","volume":"56","author":"RJ Albertini","year":"2015","unstructured":"Albertini, R. J. et al. Mutagenicity monitoring following battlefield exposures: longitudinal study of HPRT mutations in Gulf War I veterans exposed to depleted uranium. Environ. Mol. Mutagen. 56, 581\u2013593 (2015).","journal-title":"Environ. Mol. Mutagen."},{"key":"575_CR37","doi-asserted-by":"publisher","first-page":"594","DOI":"10.1002\/em.21956","volume":"56","author":"JA Nicklas","year":"2015","unstructured":"Nicklas, J. A. et al. Mutagenicity monitoring following battlefield exposures: molecular analysis of HPRT mutations in Gulf War I veterans exposed to depleted uranium. Environ. Mol. Mutagen. 56, 594\u2013608 (2015).","journal-title":"Environ. Mol. Mutagen."},{"key":"575_CR38","doi-asserted-by":"publisher","DOI":"10.1186\/gm541","volume":"6","author":"SL Poon","year":"2014","unstructured":"Poon, S. L., McPherson, J. R., Tan, P., Teh, B. T. & Rozen, S. G. Mutation signatures of carcinogen exposure: genome-wide detection and new opportunities for cancer prevention. Genome Med. 6, 24 (2014).","journal-title":"Genome Med."},{"key":"575_CR39","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms12605","volume":"7","author":"S Behjati","year":"2016","unstructured":"Behjati, S. et al. Mutational signatures of ionizing radiation in second malignancies. Nat. Commun. 7, 12605 (2016).","journal-title":"Nat. Commun."},{"key":"575_CR40","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1016\/j.dnarep.2018.08.003","volume":"71","author":"DH Phillips","year":"2018","unstructured":"Phillips, D. H. Mutational spectra and mutational signatures: insights into cancer aetiology and mechanisms of DNA damage and repair. DNA Repair 71, 6\u201311 (2018).","journal-title":"DNA Repair"},{"key":"575_CR41","doi-asserted-by":"publisher","unstructured":"Alexandrov, L. B. et al. The repertoire of mutational signatures in human cancer. Preprint at bioRxiv https:\/\/doi.org\/10.1101\/322859 (2019).","DOI":"10.1101\/322859"},{"key":"575_CR42","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1016\/j.cell.2019.03.001","volume":"177","author":"JE Kucab","year":"2019","unstructured":"Kucab, J. E. et al. A compendium of mutational signatures of environmental agents. Cell 177, 821\u2013836.e16 (2019).","journal-title":"Cell"},{"key":"575_CR43","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1038\/nature13448","volume":"513","author":"S Behjati","year":"2014","unstructured":"Behjati, S. et al. Genome sequencing of normal cells reveals developmental lineages and mutational processes. Nature 513, 422\u2013425 (2014).","journal-title":"Nature"},{"key":"575_CR44","doi-asserted-by":"publisher","first-page":"e1005932","DOI":"10.1371\/journal.pgen.1005932","volume":"12","author":"FJ Rouhani","year":"2016","unstructured":"Rouhani, F. J. et al. Mutational history of a human cell lineage from somatic to induced pluripotent stem cells. PLoS Genet. 12, e1005932 (2016).","journal-title":"PLoS Genet."},{"key":"575_CR45","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1038\/ng.3202","volume":"47","author":"A Shlien","year":"2015","unstructured":"Shlien, A. et al. Combined hereditary and somatic mutations of replication error repair genes result in rapid onset of ultra-hypermutated cancers. Nat. Genet. 47, 257\u2013262 (2015).","journal-title":"Nat. Genet."},{"key":"575_CR46","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-017-0424-2","volume":"9","author":"ZR Chalmers","year":"2017","unstructured":"Chalmers, Z. R. et al. Analysis of 100,000 human cancer genomes reveals the landscape of tumor mutational burden. Genome Med. 9, 34 (2017).","journal-title":"Genome Med."},{"key":"575_CR47","doi-asserted-by":"publisher","first-page":"1042","DOI":"10.1016\/j.cell.2017.09.048","volume":"171","author":"BB Campbell","year":"2017","unstructured":"Campbell, B. B. et al. Comprehensive analysis of hypermutation in human cancer. Cell 171, 1042\u20131056.e10 (2017).","journal-title":"Cell"},{"key":"575_CR48","doi-asserted-by":"publisher","first-page":"e32692","DOI":"10.7554\/eLife.32692","volume":"7","author":"KP Hodel","year":"2018","unstructured":"Hodel, K. P. et al. Explosive mutation accumulation triggered by heterozygous human Pol epsilon proofreading-deficiency is driven by suppression of mismatch repair. eLife 7, e32692 (2018).","journal-title":"eLife"},{"key":"575_CR49","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1038\/nrc.2015.12","volume":"16","author":"E Rayner","year":"2016","unstructured":"Rayner, E. et al. A panoply of errors: polymerase proofreading domain mutations in cancer. Nat. Rev. Cancer 16, 71\u201381 (2016).","journal-title":"Nat. Rev. Cancer"},{"key":"575_CR50","doi-asserted-by":"publisher","first-page":"2222","DOI":"10.1038\/mt.2011.191","volume":"19","author":"M Nakamori","year":"2011","unstructured":"Nakamori, M., Gourdon, G. & Thornton, C. A. Stabilization of expanded (CTG)\u00b7(CAG) repeats by antisense oligonucleotides. Mol. Ther. 19, 2222\u20132227 (2011).","journal-title":"Mol. Ther."},{"key":"575_CR51","doi-asserted-by":"publisher","first-page":"E8392","DOI":"10.1073\/pnas.1711283114","volume":"114","author":"XA Su","year":"2017","unstructured":"Su, X. A. & Freudenreich, C. H. Cytosine deamination and base excision repair cause R-loop-induced CAG repeat fragility and instability in Saccharomyces cerevisiae. Proc. Natl Acad. Sci. USA 114, E8392\u2013E8401 (2017).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"575_CR52","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1002\/mc.20488","volume":"48","author":"Y Lin","year":"2009","unstructured":"Lin, Y., Hubert, L. Jr. & Wilson, J. H. Transcription destabilizes triplet repeats. Mol. Carcinog. 48, 350\u2013361 (2009).","journal-title":"Mol. Carcinog."},{"key":"575_CR53","doi-asserted-by":"publisher","first-page":"e1000482","DOI":"10.1371\/journal.pgen.1000482","volume":"5","author":"S Tom\u00e9","year":"2009","unstructured":"Tom\u00e9, S. et al. MSH2 ATPase domain mutation affects CTG\u00b7CAG repeat instability in transgenic mice. PLoS Genet. 5, e1000482 (2009).","journal-title":"PLoS Genet."},{"key":"575_CR54","doi-asserted-by":"publisher","first-page":"1121","DOI":"10.1016\/j.dnarep.2008.03.013","volume":"7","author":"CT McMurray","year":"2008","unstructured":"McMurray, C. T. Hijacking of the mismatch repair system to cause CAG expansion and cell death in neurodegenerative disease. DNA Repair 7, 1121\u20131134 (2008).","journal-title":"DNA Repair"},{"key":"575_CR55","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.dnarep.2016.01.001","volume":"40","author":"F Morales","year":"2016","unstructured":"Morales, F. et al. A polymorphism in the MSH3 mismatch repair gene is associated with the levels of somatic instability of the expanded CTG repeat in the blood DNA of myotonic dystrophy type 1 patients. DNA Repair 40, 57\u201366 (2016).","journal-title":"DNA Repair"},{"key":"575_CR56","doi-asserted-by":"publisher","first-page":"1876","DOI":"10.1093\/brain\/awz115","volume":"142","author":"M Flower","year":"2019","unstructured":"Flower, M. et al. MSH3 modifies somatic instability and disease severity in Huntington\u2019s and myotonic dystrophy type 1. Brain 142, 1876\u20131886 (2019).","journal-title":"Brain"},{"key":"575_CR57","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1038\/nsmb959","volume":"12","author":"GB Panigrahi","year":"2005","unstructured":"Panigrahi, G. B., Lau, R., Montgomery, S. E., Leonard, M. R. & Pearson, C. E. Slipped (CTG)*(CAG) repeats can be correctly repaired, escape repair or undergo error-prone repair. Nat. Struct. Mol. Biol. 12, 654\u2013662 (2005).","journal-title":"Nat. Struct. Mol. Biol."},{"key":"575_CR58","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1016\/j.dnarep.2011.10.020","volume":"11","author":"T Zhang","year":"2012","unstructured":"Zhang, T., Huang, J., Gu, L. & Li, G. M. In vitro repair of DNA hairpins containing various numbers of CAG\/CTG trinucleotide repeats. DNA Repair 11, 201\u2013209 (2012).","journal-title":"DNA Repair"},{"key":"575_CR59","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms12465","volume":"7","author":"Y Lai","year":"2016","unstructured":"Lai, Y. et al. Crosstalk between MSH2\u2013MSH3 and pol\u03b2 promotes trinucleotide repeat expansion during base excision repair. Nat. Commun. 7, 12465 (2016).","journal-title":"Nat. Commun."},{"key":"575_CR60","doi-asserted-by":"publisher","first-page":"20452","DOI":"10.1074\/jbc.C109.014977","volume":"284","author":"L Tian","year":"2009","unstructured":"Tian, L. et al. Mismatch recognition protein MutS\u03b2 does not hijack (CAG)n hairpin repair in vitro. J. Biol. Chem. 284, 20452\u201320456 (2009).","journal-title":"J. Biol. Chem."},{"key":"575_CR61","doi-asserted-by":"publisher","first-page":"11020","DOI":"10.1038\/srep11020","volume":"5","author":"R Nakatani","year":"2015","unstructured":"Nakatani, R., Nakamori, M., Fujimura, H., Mochizuki, H. & Takahashi, M. P. Large expansion of CTG\u00b7CAG repeats is exacerbated by MutS\u03b2 in human cells. Sci. Rep. 5, 11020 (2015).","journal-title":"Sci. Rep."},{"key":"575_CR62","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1016\/j.molcel.2013.04.032","volume":"50","author":"H Chen","year":"2013","unstructured":"Chen, H., Lisby, M. & Symington, L. S. RPA coordinates DNA end resection and prevents formation of DNA hairpins. Mol. Cell 50, 589\u2013600 (2013).","journal-title":"Mol. Cell"},{"key":"575_CR63","doi-asserted-by":"publisher","first-page":"3246","DOI":"10.1016\/j.jmb.2014.07.014","volume":"426","author":"B Nguyen","year":"2014","unstructured":"Nguyen, B. et al. Diffusion of human replication protein A along single-stranded DNA. J. Mol. Biol. 426, 3246\u20133261 (2014).","journal-title":"J. Mol. Biol."},{"key":"575_CR64","doi-asserted-by":"publisher","first-page":"3883","DOI":"10.1002\/j.1460-2075.1989.tb08567.x","volume":"8","author":"T Tsurimoto","year":"1989","unstructured":"Tsurimoto, T. & Stillman, B. Multiple replication factors augment DNA synthesis by the two eukaryotic DNA polymerases, alpha and delta. EMBO J. 8, 3883\u20133889 (1989).","journal-title":"EMBO J."},{"key":"575_CR65","doi-asserted-by":"crossref","first-page":"1950","DOI":"10.1016\/S0021-9258(18)52385-1","volume":"266","author":"T Tsurimoto","year":"1991","unstructured":"Tsurimoto, T. & Stillman, B. Replication factors required for SV40 DNA replication in vitro. I. DNA structure-specific recognition of a primer\u2013template junction by eukaryotic DNA polymerases and their accessory proteins. J. Biol. Chem. 266, 1950\u20131960 (1991).","journal-title":"J. Biol. Chem."},{"key":"575_CR66","doi-asserted-by":"publisher","first-page":"30151","DOI":"10.1074\/jbc.M112.389791","volume":"287","author":"NL Chan","year":"2012","unstructured":"Chan, N. L. et al. The Werner syndrome protein promotes CAG\/CTG repeat stability by resolving large (CAG)n\/(CTG)n hairpins. J. Biol. Chem. 287, 30151\u201330156 (2012).","journal-title":"J. Biol. Chem."},{"key":"575_CR67","doi-asserted-by":"publisher","first-page":"7849","DOI":"10.1128\/MCB.23.21.7849-7860.2003","volume":"23","author":"JL Callahan","year":"2003","unstructured":"Callahan, J. L., Andrews, K. J., Zakian, V. A. & Freudenreich, C. H. Mutations in yeast replication proteins that increase CAG\/CTG expansions also increase repeat fragility. Mol. Cell. Biol. 23, 7849\u20137860 (2003).","journal-title":"Mol. Cell. Biol."},{"key":"575_CR68","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1016\/S0736-5748(02)00079-5","volume":"20","author":"NS Raji","year":"2002","unstructured":"Raji, N. S., Krishna, T. H. & Rao, K. S. DNA-polymerase \u03b1, \u03b2, \u0394 and \u03b5 activities in isolated neuronal and astroglial cell fractions from developing and aging rat cerebral cortex. Int. J. Dev. Neurosci. 20, 491\u2013496 (2002).","journal-title":"Int. J. Dev. Neurosci."},{"key":"575_CR69","doi-asserted-by":"publisher","first-page":"e44273","DOI":"10.1371\/journal.pone.0044273","volume":"7","author":"M Kovalenko","year":"2012","unstructured":"Kovalenko, M. et al. Msh2 acts in medium-spiny striatal neurons as an enhancer of CAG instability and mutant huntingtin phenotypes in Huntington\u2019s disease knock-in mice. PLoS ONE 7, e44273 (2012).","journal-title":"PLoS ONE"},{"key":"575_CR70","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1038\/ng0297-197","volume":"15","author":"L Mangiarini","year":"1997","unstructured":"Mangiarini, L. et al. Instability of highly expanded CAG repeats in mice transgenic for the Huntington\u2019s disease mutation. Nat. Genet. 15, 197\u2013200 (1997).","journal-title":"Nat. Genet."},{"key":"575_CR71","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1038\/ng.2202","volume":"44","author":"C Chiang","year":"2012","unstructured":"Chiang, C. et al. Complex reorganization and predominant non-homologous repair following chromosomal breakage in karyotypically balanced germline rearrangements and transgenic integration. Nat. Genet. 44, 390\u2013397 (2012).","journal-title":"Nat. Genet."},{"key":"575_CR72","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1016\/j.nbd.2015.01.004","volume":"76","author":"E Larson","year":"2015","unstructured":"Larson, E., Fyfe, I., Morton, A. J. & Monckton, D. G. Age-, tissue- and length-dependent bidirectional somatic CAG\u00b7CTG repeat instability in an allelic series of R6\/2 Huntington disease mice. Neurobiol. Dis. 76, 98\u2013111 (2015).","journal-title":"Neurobiol. Dis."},{"key":"575_CR73","doi-asserted-by":"publisher","first-page":"2539","DOI":"10.1093\/hmg\/9.17.2539","volume":"9","author":"L Kennedy","year":"2000","unstructured":"Kennedy, L. & Shelbourne, P. F. Dramatic mutation instability in HD mouse striatum: does polyglutamine load contribute to cell-specific vulnerability in Huntington\u2019s disease? Hum. Mol. Genet. 9, 2539\u20132544 (2000).","journal-title":"Hum. Mol. Genet."},{"key":"575_CR74","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1002\/jnr.1153","volume":"65","author":"H Ishiguro","year":"2001","unstructured":"Ishiguro, H. et al. Age-dependent and tissue-specific CAG repeat instability occurs in mouse knock-in for a mutant Huntington\u2019s disease gene. J. Neurosci. Res. 65, 289\u2013297 (2001).","journal-title":"J. Neurosci. Res."},{"key":"575_CR75","doi-asserted-by":"publisher","first-page":"3467","DOI":"10.1073\/pnas.0800048105","volume":"105","author":"R Gonitel","year":"2008","unstructured":"Gonitel, R. et al. DNA instability in postmitotic neurons. Proc. Natl Acad. Sci. USA 105, 3467\u20133472 (2008).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"575_CR76","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1007\/BF00225192","volume":"95","author":"KE De Rooij","year":"1995","unstructured":"De Rooij, K. E., De Koning Gans, P. A., Roos, R. A., Van Ommen, G. J. & Den Dunnen, J. T. Somatic expansion of the (CAG)n repeat in Huntington disease brains. Hum. Genet. 95, 270\u2013274 (1995).","journal-title":"Hum. Genet."},{"key":"575_CR77","doi-asserted-by":"publisher","first-page":"e23647","DOI":"10.1371\/journal.pone.0023647","volume":"6","author":"JM Lee","year":"2011","unstructured":"Lee, J. M., Pinto, R. M., Gillis, T., St Claire, J. C. & Wheeler, V. C. Quantification of age-dependent somatic CAG repeat instability in Hdh CAG knock-in mice reveals different expansion dynamics in striatum and liver. PLoS ONE 6, e23647 (2011).","journal-title":"PLoS ONE"},{"key":"575_CR78","doi-asserted-by":"publisher","DOI":"10.1186\/1752-0509-4-29","volume":"4","author":"JM Lee","year":"2010","unstructured":"Lee, J. M. et al. A novel approach to investigate tissue-specific trinucleotide repeat instability. BMC Syst. Biol. 4, 29 (2010).","journal-title":"BMC Syst. Biol."},{"key":"575_CR79","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1136\/jmg.2007.050930","volume":"44","author":"VC Wheeler","year":"2007","unstructured":"Wheeler, V. C. et al. Factors associated with HD CAG repeat instability in Huntington disease. J. Med. Genet. 44, 695\u2013701 (2007).","journal-title":"J. Med. Genet."},{"key":"575_CR80","doi-asserted-by":"publisher","first-page":"2450","DOI":"10.1093\/hmg\/dds059","volume":"21","author":"CF Higham","year":"2012","unstructured":"Higham, C. F., Morales, F., Cobbold, C. A., Haydon, D. T. & Monckton, D. G. High levels of somatic DNA diversity at the myotonic dystrophy type 1 locus are driven by ultra-frequent expansion and contraction mutations. Hum. Mol. Genet. 21, 2450\u20132463 (2012).","journal-title":"Hum. Mol. Genet."},{"key":"575_CR81","doi-asserted-by":"publisher","first-page":"789","DOI":"10.1016\/j.dnarep.2007.01.002","volume":"6","author":"NJ Veitch","year":"2007","unstructured":"Veitch, N. J. et al. Inherited CAG.CTG allele length is a major modifier of somatic mutation length variability in Huntington disease. DNA Repair 6, 789\u2013796 (2007).","journal-title":"DNA Repair"},{"key":"575_CR82","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1007\/978-1-60327-409-8_5","volume":"682","author":"PJ Hornsby","year":"2011","unstructured":"Hornsby, P. J. & Didenko, V. V. In situ ligation: a decade and a half of experience. Methods Mol. Biol. 682, 49\u201363 (2011).","journal-title":"Methods Mol. Biol."},{"key":"575_CR83","doi-asserted-by":"publisher","first-page":"1469","DOI":"10.1007\/s11033-018-4258-9","volume":"45","author":"P Majtnerova","year":"2018","unstructured":"Majtnerova, P. & Rousar, T. An overview of apoptosis assays detecting DNA fragmentation. Mol. Biol. Rep. 45, 1469\u20131478 (2018).","journal-title":"Mol. Biol. Rep."},{"key":"575_CR84","doi-asserted-by":"publisher","first-page":"830","DOI":"10.1046\/j.1471-4159.2000.0750830.x","volume":"75","author":"C Iannicola","year":"2000","unstructured":"Iannicola, C. et al. Early alterations in gene expression and cell morphology in a mouse model of Huntington\u2019s disease. J. Neurochem. 75, 830\u2013839 (2000).","journal-title":"J. Neurochem."},{"key":"575_CR85","doi-asserted-by":"publisher","first-page":"8093","DOI":"10.1073\/pnas.110078997","volume":"97","author":"M Turmaine","year":"2000","unstructured":"Turmaine, M. et al. Nonapoptotic neurodegeneration in a transgenic mouse model of Huntington\u2019s disease. Proc. Natl Acad. Sci. USA 97, 8093\u20138097 (2000).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"575_CR86","doi-asserted-by":"publisher","first-page":"2193","DOI":"10.1523\/JNEUROSCI.23-06-02193.2003","volume":"23","author":"ZX Yu","year":"2003","unstructured":"Yu, Z. X. et al. Mutant huntingtin causes context-dependent neurodegeneration in mice with Huntington\u2019s disease. J. Neurosci. 23, 2193\u20132202 (2003).","journal-title":"J. Neurosci."},{"key":"575_CR87","doi-asserted-by":"publisher","first-page":"1990","DOI":"10.1126\/science.277.5334.1990","volume":"277","author":"M DiFiglia","year":"1997","unstructured":"DiFiglia, M. et al. Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain. Science 277, 1990\u20131993 (1997).","journal-title":"Science"},{"key":"575_CR88","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1093\/hmg\/7.5.777","volume":"7","author":"SH Li","year":"1998","unstructured":"Li, S. H. & Li, X. J. Aggregation of N-terminal huntingtin is dependent on the length of its glutamine repeats. Hum. Mol. Genet. 7, 777\u2013782 (1998).","journal-title":"Hum. Mol. Genet."},{"key":"575_CR89","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1006\/nbdi.1998.0168","volume":"4","author":"MW Becher","year":"1998","unstructured":"Becher, M. W. et al. Intranuclear neuronal inclusions in Huntington\u2019s disease and dentatorubral and pallidoluysian atrophy: correlation between the density of inclusions and IT15 CAG triplet repeat length. Neurobiol. Dis. 4, 387\u2013397 (1998).","journal-title":"Neurobiol. Dis."},{"key":"575_CR90","doi-asserted-by":"publisher","first-page":"1227","DOI":"10.1093\/hmg\/8.7.1227","volume":"8","author":"H Li","year":"1999","unstructured":"Li, H. et al. Ultrastructural localization and progressive formation of neuropil aggregates in Huntington\u2019s disease transgenic mice. Hum. Mol. Genet. 8, 1227\u20131236 (1999).","journal-title":"Hum. Mol. Genet."},{"key":"575_CR91","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1038\/78054","volume":"25","author":"H Li","year":"2000","unstructured":"Li, H., Li, S. H., Johnston, H., Shelbourne, P. F. & Li, X. J. Amino-terminal fragments of mutant huntingtin show selective accumulation in striatal neurons and synaptic toxicity. Nat. Genet. 25, 385\u2013389 (2000).","journal-title":"Nat. Genet."},{"key":"575_CR92","doi-asserted-by":"publisher","first-page":"e0123527","DOI":"10.1371\/journal.pone.0123527","volume":"10","author":"N Carty","year":"2015","unstructured":"Carty, N. et al. Characterization of HTT inclusion size, location, and timing in the zQ175 mouse model of Huntington\u2019s disease: an in vivo high-content imaging study. PLoS ONE 10, e0123527 (2015).","journal-title":"PLoS ONE"},{"key":"575_CR93","doi-asserted-by":"publisher","first-page":"962","DOI":"10.1111\/j.1471-4159.2004.02376.x","volume":"89","author":"MD Kaytor","year":"2004","unstructured":"Kaytor, M. D., Wilkinson, K. D. & Warren, S. T. Modulating huntingtin half-life alters polyglutamine-dependent aggregate formation and cell toxicity. J. Neurochem. 89, 962\u2013973 (2004).","journal-title":"J. Neurochem."},{"key":"575_CR94","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1177\/1087057107299428","volume":"12","author":"M Coufal","year":"2007","unstructured":"Coufal, M. et al. Discovery of a novel small-molecule targeting selective clearance of mutant huntingtin fragments. J. Biomol. Screen. 12, 351\u2013360 (2007).","journal-title":"J. Biomol. Screen."},{"key":"575_CR95","doi-asserted-by":"publisher","first-page":"16685","DOI":"10.1073\/pnas.0707842104","volume":"104","author":"V Chopra","year":"2007","unstructured":"Chopra, V. et al. A small-molecule therapeutic lead for Huntington\u2019s disease: preclinical pharmacology and efficacy of C2-8 in the R6\/2 transgenic mouse. Proc. Natl Acad. Sci. USA 104, 16685\u201316689 (2007).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"575_CR96","doi-asserted-by":"publisher","first-page":"e29199","DOI":"10.1371\/journal.pone.0029199","volume":"6","author":"DC Butler","year":"2011","unstructured":"Butler, D. C. & Messer, A. Bifunctional anti-huntingtin proteasome-directed intrabodies mediate efficient degradation of mutant huntingtin exon 1 protein fragments. PLoS ONE 6, e29199 (2011).","journal-title":"PLoS ONE"},{"key":"575_CR97","doi-asserted-by":"publisher","first-page":"e73120","DOI":"10.1371\/journal.pone.0073120","volume":"8","author":"J Perucho","year":"2013","unstructured":"Perucho, J. et al. Striatal infusion of glial conditioned medium diminishes huntingtin pathology in r6\/1 mice. PLoS ONE 8, e73120 (2013).","journal-title":"PLoS ONE"},{"key":"575_CR98","doi-asserted-by":"publisher","first-page":"586","DOI":"10.1038\/nchembio.1308","volume":"9","author":"AS Tsvetkov","year":"2013","unstructured":"Tsvetkov, A. S. et al. Proteostasis of polyglutamine varies among neurons and predicts neurodegeneration. Nat. Chem. Biol. 9, 586\u2013592 (2013).","journal-title":"Nat. Chem. Biol."},{"key":"575_CR99","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1002\/ana.410410521","volume":"41","author":"JB Penney Jr","year":"1997","unstructured":"Penney, J. B. Jr, Vonsattel, J. P., MacDonald, M. E., Gusella, J. F. & Myers, R. H. CAG repeat number governs the development rate of pathology in Huntington\u2019s disease. Ann. Neurol. 41, 689\u2013692 (1997).","journal-title":"Ann. Neurol."},{"key":"575_CR100","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1093\/hmg\/9.4.503","volume":"9","author":"VC Wheeler","year":"2000","unstructured":"Wheeler, V. C. et al. Long glutamine tracts cause nuclear localization of a novel form of huntingtin in medium spiny striatal neurons in HdhQ92 and HdhQ111 knock-in mice. Hum. Mol. Genet. 9, 503\u2013513 (2000).","journal-title":"Hum. Mol. Genet."},{"key":"575_CR101","doi-asserted-by":"publisher","first-page":"708","DOI":"10.1002\/ana.410440424","volume":"44","author":"A Rosenblatt","year":"1998","unstructured":"Rosenblatt, A. et al. Does CAG repeat number predict the rate of pathological changes in Huntington\u2019s disease? Ann. Neurol. 44, 708\u2013709 (1998).","journal-title":"Ann. Neurol."},{"key":"575_CR102","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1016\/S1474-4422(17)30280-6","volume":"16","author":"EJ Wild","year":"2017","unstructured":"Wild, E. J. & Tabrizi, S. J. Therapies targeting DNA and RNA in Huntington\u2019s disease. Lancet Neurol. 16, 837\u2013847 (2017).","journal-title":"Lancet Neurol."},{"key":"575_CR103","doi-asserted-by":"publisher","unstructured":"Dabrowska, M., Juzwa, W., Krzyzosiak, W. J. & Olejniczak, M. Precise excision of the CAG tract from the Huntingtin gene by Cas9 nickases. Front. Neurosci. https:\/\/doi.org\/10.3389\/fnins.2018.00075 (2018).","DOI":"10.3389\/fnins.2018.00075"},{"key":"575_CR104","first-page":"4566","volume":"25","author":"JW Shin","year":"2016","unstructured":"Shin, J. W. et al. Permanent inactivation of Huntington\u2019s disease mutation by personalized allele-specific CRISPR\/Cas9. Hum. Mol. Genet. 25, 4566\u20134576 (2016).","journal-title":"Hum. Mol. Genet."},{"key":"575_CR105","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.ymthe.2016.11.010","volume":"25","author":"AM Monteys","year":"2017","unstructured":"Monteys, A. M., Ebanks, S. A., Keiser, M. S. & Davidson, B. L. CRISPR\/Cas9 editing of the mutant huntingtin allele in vitro and in vivo. Mol. Ther. 25, 12\u201323 (2017).","journal-title":"Mol. Ther."},{"key":"575_CR106","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms13272","volume":"7","author":"C Cinesi","year":"2016","unstructured":"Cinesi, C., Aeschbach, L., Yang, B. & Dion, V. Contracting CAG\/CTG repeats using the CRISPR\u2013Cas9 nickase. Nat. Commun. 7, 13272 (2016).","journal-title":"Nat. Commun."},{"key":"575_CR107","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-05125-2","volume":"7","author":"N Suelves","year":"2017","unstructured":"Suelves, N., Kirkham-McCarthy, L., Lahue, R. S. & Gines, S. A selective inhibitor of histone deacetylase 3 prevents cognitive deficits and suppresses striatal CAG repeat expansions in Huntington\u2019s disease mice. Sci. Rep. 7, 6082 (2017).","journal-title":"Sci. Rep."},{"key":"575_CR108","doi-asserted-by":"publisher","first-page":"S42","DOI":"10.1038\/d41586-018-05177-y","volume":"557","author":"M Eisenstein","year":"2018","unstructured":"Eisenstein, M. CRISPR takes on Huntington\u2019s disease. Nature 557, S42\u2013S43 (2018).","journal-title":"Nature"},{"key":"575_CR109","doi-asserted-by":"publisher","first-page":"1311","DOI":"10.1007\/s00439-014-1467-8","volume":"133","author":"S Martins","year":"2014","unstructured":"Martins, S. et al. Modifiers of (CAG)n instability in Machado\u2013Joseph disease (MJD\/SCA3) transmissions: an association study with DNA replication, repair and recombination genes. Hum. Genet. 133, 1311\u20131318 (2014).","journal-title":"Hum. Genet."},{"key":"575_CR110","doi-asserted-by":"publisher","first-page":"775","DOI":"10.1038\/cr.2016.66","volume":"26","author":"J Guo","year":"2016","unstructured":"Guo, J., Gu, L., Leffak, M. & Li, G. M. MutS\u03b2 promotes trinucleotide repeat expansion by recruiting DNA polymerase \u03b2 to nascent (CAG)n or (CTG)n hairpins for error-prone DNA synthesis. Cell Res. 26, 775\u2013786 (2016).","journal-title":"Cell Res."},{"key":"575_CR111","doi-asserted-by":"publisher","first-page":"958","DOI":"10.1038\/nrm2549","volume":"9","author":"PC Hanawalt","year":"2008","unstructured":"Hanawalt, P. C. & Spivak, G. Transcription-coupled DNA repair: two decades of progress and surprises. Nat. Rev. Mol. Cell Biol. 9, 958\u2013970 (2008).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"575_CR112","doi-asserted-by":"publisher","first-page":"869","DOI":"10.1038\/nsmb.1638","volume":"16","author":"C Hou","year":"2009","unstructured":"Hou, C., Chan, N. L., Gu, L. & Li, G. M. Incision-dependent and error-free repair of (CAG)n\/(CTG)n hairpins in human cell extracts. Nat. Struct. Mol. Biol. 16, 869\u2013875 (2009).","journal-title":"Nat. Struct. Mol. Biol."},{"key":"575_CR113","doi-asserted-by":"publisher","first-page":"15015","DOI":"10.1074\/jbc.M113.464370","volume":"288","author":"NL Chan","year":"2013","unstructured":"Chan, N. L. et al. Coordinated processing of 3\u2032 slipped (CAG)n\/(CTG)n hairpins by DNA polymerases \u03b2 and \u0394 preferentially induces repeat expansions. J. Biol. Chem. 288, 15015\u201315022 (2013).","journal-title":"J. Biol. Chem."},{"key":"575_CR114","doi-asserted-by":"publisher","first-page":"e1003930","DOI":"10.1371\/journal.pgen.1003930","volume":"9","author":"RM Pinto","year":"2013","unstructured":"Pinto, R. M. et al. Mismatch repair genes Mlh1 and Mlh3 modify CAG instability in Huntington\u2019s disease mice: genome-wide and candidate approaches. PLoS Genet. 9, e1003930 (2013).","journal-title":"PLoS Genet."},{"key":"575_CR115","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1093\/hmg\/ddg056","volume":"12","author":"VC Wheeler","year":"2003","unstructured":"Wheeler, V. C. et al. Mismatch repair gene Msh2 modifies the timing of early disease in Hdh\nQ111 striatum. Hum. Mol. Genet. 12, 273\u2013281 (2003).","journal-title":"Hum. Mol. Genet."},{"key":"575_CR116","doi-asserted-by":"publisher","first-page":"1639","DOI":"10.1126\/science.1836279","volume":"254","author":"SA Strobel","year":"1991","unstructured":"Strobel, S. A., Doucette-Stamm, L. A., Riba, L., Housman, D. E. & Dervan, P. B. Site-specific cleavage of human chromosome 4 mediated by triple-helix formation. Science 254, 1639\u20131642 (1991).","journal-title":"Science"},{"key":"575_CR117","doi-asserted-by":"publisher","first-page":"9607","DOI":"10.1073\/pnas.0902420106","volume":"106","author":"D Mittelman","year":"2009","unstructured":"Mittelman, D. et al. Zinc-finger directed double-strand breaks within CAG repeat tracts promote repeat instability in human cells. Proc. Natl Acad. Sci. USA 106, 9607\u20139612 (2009).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"575_CR118","doi-asserted-by":"publisher","first-page":"1131","DOI":"10.1038\/s41591-019-0478-3","volume":"25","author":"B Zeitler","year":"2019","unstructured":"Zeitler, B. et al. Allele-selective transcriptional repression of mutant HTT for the treatment of Huntington\u2019s disease. Nat. Med. 25, 1131\u20131142 (2019).","journal-title":"Nat. Med."},{"key":"575_CR119","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1007\/s00294-018-0865-1","volume":"65","author":"V Mosbach","year":"2019","unstructured":"Mosbach, V., Poggi, L. & Richard, G. F. Trinucleotide repeat instability during double-strand break repair: from mechanisms to gene therapy. Curr. Genet. 65, 17\u201328 (2019).","journal-title":"Curr. Genet."},{"key":"575_CR120","doi-asserted-by":"publisher","first-page":"19","DOI":"10.3233\/JHD-160222","volume":"6","author":"TB Malankhanova","year":"2017","unstructured":"Malankhanova, T. B., Malakhova, A. A., Medvedev, S. P. & Zakian, S. M. Modern genome editing technologies in Huntington\u2019s disease research. J. Huntington\u2019s Dis. 6, 19\u201331 (2017).","journal-title":"J. Huntington\u2019s Dis."},{"key":"575_CR121","doi-asserted-by":"publisher","first-page":"e0212198","DOI":"10.1371\/journal.pone.0212198","volume":"14","author":"H Babacic","year":"2019","unstructured":"Babacic, H., Mehta, A., Merkel, O. & Schoser, B. CRISPR-cas gene-editing as plausible treatment of neuromuscular and nucleotide-repeat-expansion diseases: a systematic review. PLoS ONE 14, e0212198 (2019).","journal-title":"PLoS ONE"},{"key":"575_CR122","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.mrfmmm.2006.01.011","volume":"598","author":"M Gomes-Pereira","year":"2006","unstructured":"Gomes-Pereira, M. & Monckton, D. G. Chemical modifiers of unstable expanded simple sequence repeats: what goes up, could come down. Mutat. Res. 598, 15\u201334 (2006).","journal-title":"Mutat. Res."},{"key":"575_CR123","doi-asserted-by":"publisher","first-page":"6733","DOI":"10.1093\/nar\/gkg898","volume":"31","author":"E Pineiro","year":"2003","unstructured":"Pineiro, E. et al. Mutagenic stress modulates the dynamics of CTG repeat instability associated with myotonic dystrophy type 1. Nucleic Acids Res. 31, 6733\u20136740 (2003).","journal-title":"Nucleic Acids Res."},{"key":"575_CR124","doi-asserted-by":"publisher","first-page":"e1005267","DOI":"10.1371\/journal.pgen.1005267","volume":"11","author":"H Budworth","year":"2015","unstructured":"Budworth, H. et al. Suppression of somatic expansion delays the onset of pathophysiology in a mouse model of Huntington\u2019s disease. PLoS Genet. 11, e1005267 (2015).","journal-title":"PLoS Genet."},{"key":"575_CR125","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1038\/387202a0","volume":"387","author":"JM Gottesfeld","year":"1997","unstructured":"Gottesfeld, J. M., Neely, L., Trauger, J. W., Baird, E. E. & Dervan, P. B. Regulation of gene expression by small molecules. Nature 387, 202\u2013205 (1997).","journal-title":"Nature"},{"key":"575_CR126","doi-asserted-by":"publisher","first-page":"3063","DOI":"10.4161\/cc.26130","volume":"12","author":"OV Leontieva","year":"2013","unstructured":"Leontieva, O. V. & Blagosklonny, M. V. CDK4\/6-inhibiting drug substitutes for p21 and p16 in senescence: duration of cell cycle arrest and MTOR activity determine geroconversion. Cell Cycle 12, 3063\u20133069 (2013).","journal-title":"Cell Cycle"},{"key":"575_CR127","doi-asserted-by":"publisher","first-page":"759","DOI":"10.1016\/j.nmd.2009.07.012","volume":"19","author":"M Nakamori","year":"2009","unstructured":"Nakamori, M., Sobczak, K., Moxley, R. T. & Thornton, C. A. Scaled-down genetic analysis of myotonic dystrophy type 1 and type 2. Neuromuscul. Disord. 19, 759\u2013762 (2009).","journal-title":"Neuromuscul. Disord."},{"key":"575_CR128","first-page":"385","volume":"69","author":"JD Brook","year":"1992","unstructured":"Brook, J. D. et al. Molecular basis of myotonic dystrophy: expansion of a trinucleotide (CTG) repeat at the 3\u2032 end of a transcript encoding a protein kinase family member. Cell 69, 385 (1992).","journal-title":"Cell"},{"key":"575_CR129","first-page":"4749","volume":"57","author":"W Dietmaier","year":"1997","unstructured":"Dietmaier, W. et al. Diagnostic microsatellite instability: definition and correlation with mismatch repair protein expression. Cancer Res. 57, 4749\u20134756 (1997).","journal-title":"Cancer Res."},{"key":"575_CR130","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1002\/mc.10157","volume":"38","author":"O Kabbarah","year":"2003","unstructured":"Kabbarah, O. et al. A panel of repeat markers for detection of microsatellite instability in murine tumors. Mol. Carcinog. 38, 155\u2013159 (2003).","journal-title":"Mol. Carcinog."},{"key":"575_CR131","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1038\/7710","volume":"21","author":"MD Koob","year":"1999","unstructured":"Koob, M. D. et al. An untranslated CTG expansion causes a novel form of spinocerebellar ataxia (SCA8). Nat. Genet. 21, 379\u2013384 (1999).","journal-title":"Nat. Genet."},{"key":"575_CR132","first-page":"343","volume":"57","author":"B Kremer","year":"1995","unstructured":"Kremer, B. et al. Sex-dependent mechanisms for expansions and contractions of the CAG repeat on affected Huntington disease chromosomes. Am. J. Hum. Genet. 57, 343\u2013350 (1995).","journal-title":"Am. J. Hum. Genet."},{"key":"575_CR133","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1038\/ng870","volume":"31","author":"JD Cleary","year":"2002","unstructured":"Cleary, J. D., Nichol, K., Wang, Y. H. & Pearson, C. E. Evidence of cis-acting factors in replication-mediated trinucleotide repeat instability in primate cells. Nat. Genet. 31, 37\u201346 (2002).","journal-title":"Nat. Genet."},{"key":"575_CR134","doi-asserted-by":"publisher","first-page":"13926","DOI":"10.1074\/jbc.M109761200","volume":"277","author":"GB Panigrahi","year":"2002","unstructured":"Panigrahi, G. B., Cleary, J. D. & Pearson, C. E. In vitro (CTG)*(CAG) expansions and deletions by human cell extracts. J. Biol. Chem. 277, 13926\u201313934 (2002).","journal-title":"J. Biol. Chem."},{"key":"575_CR135","doi-asserted-by":"publisher","first-page":"1749","DOI":"10.1093\/nar\/gkq935","volume":"39","author":"K Reddy","year":"2011","unstructured":"Reddy, K. et al. Determinants of R-loop formation at convergent bidirectionally transcribed trinucleotide repeats. Nucleic Acids Res. 39, 1749\u20131762 (2011).","journal-title":"Nucleic Acids Res."},{"key":"575_CR136","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/S0076-6879(05)09002-6","volume":"409","author":"SK Binz","year":"2006","unstructured":"Binz, S. K., Dickson, A. M., Haring, S. J. & Wold, M. S. Functional assays for replication protein A (RPA). Methods Enzymol. 409, 11\u201338 (2006).","journal-title":"Methods Enzymol."},{"key":"575_CR137","doi-asserted-by":"publisher","first-page":"e39156","DOI":"10.1371\/journal.pone.0039156","volume":"7","author":"Y Zhou","year":"2012","unstructured":"Zhou, Y., Meng, X., Zhang, S., Lee, E. Y. & Lee, M. Y. Characterization of human DNA polymerase delta and its subassemblies reconstituted by expression in the MultiBac system. PLoS ONE 7, e39156 (2012).","journal-title":"PLoS ONE"},{"key":"575_CR138","doi-asserted-by":"publisher","first-page":"5919","DOI":"10.1021\/bi100380n","volume":"49","author":"AC Mason","year":"2010","unstructured":"Mason, A. C., Roy, R., Simmons, D. T. & Wold, M. S. Functions of alternative replication protein A in initiation and elongation. Biochemistry 49, 5919\u20135928 (2010).","journal-title":"Biochemistry"},{"key":"575_CR139","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/j.dnarep.2012.10.006","volume":"12","author":"S Tome","year":"2013","unstructured":"Tome, S. et al. Tissue-specific mismatch repair protein expression: MSH3 is higher than MSH6 in multiple mouse tissues. DNA Repair 12, 46\u201352 (2013).","journal-title":"DNA Repair"},{"key":"575_CR140","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1007\/s00401-016-1582-9","volume":"132","author":"I Jeon","year":"2016","unstructured":"Jeon, I. et al. Human-to-mouse prion-like propagation of mutant huntingtin protein. Acta Neuropathol. 132, 577\u2013592 (2016).","journal-title":"Acta Neuropathol."},{"key":"575_CR141","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1038\/nbt.2514","volume":"31","author":"K Cibulskis","year":"2013","unstructured":"Cibulskis, K. et al. Sensitive detection of somatic point mutations in impure and heterogeneous cancer samples. Nat. Biotechnol. 31, 213\u2013219 (2013).","journal-title":"Nat. Biotechnol."},{"key":"575_CR142","doi-asserted-by":"publisher","first-page":"1028","DOI":"10.1089\/cmb.2006.13.1028","volume":"13","author":"A Morgulis","year":"2006","unstructured":"Morgulis, A., Gertz, E. M., Schaffer, A. A. & Agarwala, R. A fast and symmetric DUST implementation to mask low-complexity DNA sequences. J. Comput. Biol. 13, 1028\u20131040 (2006).","journal-title":"J. Comput. Biol."},{"key":"575_CR143","doi-asserted-by":"publisher","first-page":"2843","DOI":"10.1093\/bioinformatics\/btu356","volume":"30","author":"H Li","year":"2014","unstructured":"Li, H. Toward better understanding of artifacts in variant calling from high-coverage samples. Bioinformatics 30, 2843\u20132851 (2014).","journal-title":"Bioinformatics"},{"key":"575_CR144","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1038\/nature12477","volume":"500","author":"LB Alexandrov","year":"2013","unstructured":"Alexandrov, L. B. et al. Signatures of mutational processes in human cancer. Nature 500, 415\u2013421 (2013).","journal-title":"Nature"},{"key":"575_CR145","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1016\/j.celrep.2012.12.008","volume":"3","author":"LB Alexandrov","year":"2013","unstructured":"Alexandrov, L. B., Nik-Zainal, S., Wedge, D. C., Campbell, P. J. & Stratton, M. R. Deciphering signatures of mutational processes operative in human cancer. Cell Rep. 3, 246\u2013259 (2013).","journal-title":"Cell Rep."},{"key":"575_CR146","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1038\/nature17676","volume":"534","author":"S Nik-Zainal","year":"2016","unstructured":"Nik-Zainal, S. et al. Landscape of somatic mutations in 560 breast cancer whole-genome sequences. Nature 534, 47\u201354 (2016).","journal-title":"Nature"},{"key":"575_CR147","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1093\/bioinformatics\/btp698","volume":"26","author":"H Li","year":"2010","unstructured":"Li, H. & Durbin, R. Fast and accurate long-read alignment with Burrows\u2013Wheeler transform. Bioinformatics 26, 589\u2013595 (2010).","journal-title":"Bioinformatics"}],"container-title":["Nature Genetics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/s41588-019-0575-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/s41588-019-0575-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/s41588-019-0575-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,20]],"date-time":"2023-05-20T18:23:21Z","timestamp":1684607001000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41588-019-0575-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,2]]},"references-count":147,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2020,2]]}},"alternative-id":["575"],"URL":"https:\/\/doi.org\/10.1038\/s41588-019-0575-8","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.737369691.793575486","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.737369691.793571134","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.737369691.793574362","asserted-by":"object"}]},"ISSN":["1061-4036","1546-1718"],"issn-type":[{"value":"1061-4036","type":"print"},{"value":"1546-1718","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,2]]},"assertion":[{"value":"20 October 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 December 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 February 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}