{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T12:37:57Z","timestamp":1765888677266,"version":"build-2065373602"},"reference-count":146,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2021,8,25]],"date-time":"2021-08-25T00:00:00Z","timestamp":1629849600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["1ZIADK057602"],"award-info":[{"award-number":["1ZIADK057602"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Fragile X-related disorders (FXDs), also known as FMR1 disorders, are examples of repeat expansion diseases (REDs), clinical conditions that arise from an increase in the number of repeats in a disease-specific microsatellite. In the case of FXDs, the repeat unit is CGG\/CCG and the repeat tract is located in the 5\u2032 UTR of the X-linked FMR1 gene. Expansion can result in neurodegeneration, ovarian dysfunction, or intellectual disability depending on the number of repeats in the expanded allele. A growing body of evidence suggests that the mutational mechanisms responsible for many REDs share several common features. It is also increasingly apparent that in some of these diseases the pathologic consequences of expansion may arise in similar ways. It has long been known that many of the disease-associated repeats form unusual DNA and RNA structures. This review will focus on what is known about these structures, the proteins with which they interact, and how they may be related to the causative mutation and disease pathology in the FMR1 disorders.<\/jats:p>","DOI":"10.3390\/ijms22179167","type":"journal-article","created":{"date-parts":[[2021,8,26]],"date-time":"2021-08-26T00:19:26Z","timestamp":1629937166000},"page":"9167","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["(Dys)function Follows Form: Nucleic Acid Structure, Repeat Expansion, and Disease Pathology in FMR1 Disorders"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7281-3914","authenticated-orcid":false,"given":"Xiaonan","family":"Zhao","sequence":"first","affiliation":[{"name":"Laboratory of Cell and Molecular Biology, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen","family":"Usdin","sequence":"additional","affiliation":[{"name":"Laboratory of Cell and Molecular Biology, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/B978-0-444-63233-3.00009-9","article-title":"Repeat expansion diseases","volume":"147","author":"Paulson","year":"2018","journal-title":"Handb. Clin. Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1007\/978-1-4614-5434-2_6","article-title":"Unstable mutations in the FMR1 gene and the phenotypes","volume":"769","author":"Loesch","year":"2012","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1038\/s41593-020-0590-1","article-title":"A native function for RAN translation and CGG repeats in regulating fragile X protein synthesis","volume":"23","author":"Rodriguez","year":"2020","journal-title":"Nat. Neurosci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.1002\/ajmg.a.61165","article-title":"Expansions and contractions of the FMR1 CGG repeat in 5508 transmissions of normal, intermediate, and premutation alleles","volume":"179","author":"Nolin","year":"2019","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1002\/humu.22177","article-title":"Somatic expansion in mouse and human carriers of fragile X premutation alleles","volume":"34","author":"Lokanga","year":"2013","journal-title":"Hum. Mutat."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1016\/j.ebiom.2019.09.020","article-title":"A genetic association study of glutamine-encoding DNA sequence structures, somatic CAG expansion, and DNA repair gene variants, with Huntington disease clinical outcomes","volume":"48","author":"Ciosi","year":"2019","journal-title":"EBioMedicine"},{"unstructured":"Genetic Modifiers of Huntington\u2019s Disease Consortium (2019). CAG Repeat Not Polyglutamine Length Determines Timing of Huntington\u2019s Disease Onset. Cell, 178, 887\u2013900.e814.","key":"ref_7"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1086\/302720","article-title":"Elevated levels of FMR1 mRNA in carrier males: A new mechanism of involvement in the fragile-X syndrome","volume":"66","author":"Tassone","year":"2000","journal-title":"Am. J. Hum. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1016\/0092-8674(91)90283-5","article-title":"Variation of the CGG repeat at the fragile X site results in genetic instability: Resolution of the Sherman paradox","volume":"67","author":"Fu","year":"1991","journal-title":"Cell"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1016\/0092-8674(91)90397-H","article-title":"Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome","volume":"65","author":"Verkerk","year":"1991","journal-title":"Cell"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1097\/WCO.0000000000000954","article-title":"Fragile X-associated tremor\/ataxia syndrome: Pathophysiology and management","volume":"34","author":"Hagerman","year":"2021","journal-title":"Curr. Opin. Neurol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1038\/s41436-019-0733-5","article-title":"Clustering of comorbid conditions among women who carry an FMR1 premutation","volume":"22","author":"Allen","year":"2020","journal-title":"Genet. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1038\/sj.ejhg.5201510","article-title":"Nonlinear association between CGG repeat number and age of menopause in FMR1 premutation carriers","volume":"14","author":"Ennis","year":"2006","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1093\/humrep\/deh635","article-title":"Association of FMR1 repeat size with ovarian dysfunction","volume":"20","author":"Sullivan","year":"2005","journal-title":"Hum. Reprod."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1016\/j.bbagrm.2017.08.007","article-title":"Altered expression of the FMR1 splicing variants landscape in premutation carriers","volume":"1860","author":"Tseng","year":"2017","journal-title":"Biochim. Biophys. Acta Gene Regul. Mech."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3661","DOI":"10.1093\/hmg\/ddi394","article-title":"Induction of inclusion formation and disruption of lamin A\/C structure by premutation CGG-repeat RNA in human cultured neural cells","volume":"14","author":"Arocena","year":"2005","journal-title":"Hum. Mol. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1093\/brain\/awh650","article-title":"Protein composition of the intranuclear inclusions of FXTAS","volume":"129","author":"Iwahashi","year":"2006","journal-title":"Brain"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1186\/s40478-019-0796-1","article-title":"Composition of the Intranuclear Inclusions of Fragile X-associated Tremor\/Ataxia Syndrome","volume":"7","author":"Ma","year":"2019","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/1866-1955-6-24","article-title":"AGG interruptions and maternal age affect FMR1 CGG repeat allele stability during transmission","volume":"6","author":"Yrigollen","year":"2014","journal-title":"J. Neurodev. Disord."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1038\/ng0693-143","article-title":"The full mutation in the FMR-1 gene of male fragile X patients is absent in their sperm","volume":"4","author":"Reyniers","year":"1993","journal-title":"Nat. Genet."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"145","DOI":"10.5582\/irdr.2016.01048","article-title":"Fragile X syndrome: A review of clinical management","volume":"5","author":"Lozano","year":"2016","journal-title":"Intractable Rare Dis. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"17065","DOI":"10.1038\/nrdp.2017.65","article-title":"Fragile X syndrome","volume":"3","author":"Hagerman","year":"2017","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1038\/s41583-021-00432-0","article-title":"The molecular biology of FMRP: New insights into fragile X syndrome","volume":"22","author":"Richter","year":"2021","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2152","DOI":"10.1002\/ajmg.a.33011","article-title":"Fragile X prenatal analyses show full mutation females at high risk for mosaic Turner syndrome: Fragile X leads to chromosome loss","volume":"149A","author":"Dobkin","year":"2009","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/S0092-8674(01)00566-9","article-title":"Fragile X mental retardation protein targets G quartet mRNAs important for neuronal function","volume":"107","author":"Darnell","year":"2001","journal-title":"Cell"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"108838","DOI":"10.1016\/j.celrep.2021.108838","article-title":"Replication stress induces global chromosome breakage in the fragile X genome","volume":"34","author":"Chakraborty","year":"2021","journal-title":"Cell Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"4202","DOI":"10.1093\/nar\/23.20.4202","article-title":"CGG repeats associated with DNA instability and chromosome fragility form structures that block DNA synthesis in vitro","volume":"23","author":"Usdin","year":"1995","journal-title":"Nucleic Acids Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"12803","DOI":"10.1021\/bi00039a041","article-title":"The trinucleotide repeat sequence d(CGG)15 forms a heat-stable hairpin containing Gsyn. Ganti base pairs","volume":"34","author":"Mitas","year":"1995","journal-title":"Biochemistry"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3687","DOI":"10.1021\/bi9625410","article-title":"At physiological pH, d(CCG)15 forms a hairpin containing protonated cytosines and a distorted helix","volume":"36","author":"Yu","year":"1997","journal-title":"Biochemistry"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"28970","DOI":"10.1074\/jbc.270.48.28970","article-title":"The fragile X syndrome single strand d(CGG)n nucleotide repeats readily fold back to form unimolecular hairpin structures","volume":"270","author":"Nadel","year":"1995","journal-title":"J. Biol. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"5199","DOI":"10.1073\/pnas.92.11.5199","article-title":"Hairpins are formed by the single DNA strands of the fragile X triplet repeats: Structure and biological implications","volume":"92","author":"Chen","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/0092-8674(95)90074-8","article-title":"Trinucleotide repeats that expand in human disease form hairpin structures in vitro","volume":"81","author":"Gacy","year":"1995","journal-title":"Cell"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2245","DOI":"10.1093\/nar\/25.12.2245","article-title":"Trinucleotide repeats associated with human disease","volume":"25","author":"Mitas","year":"1997","journal-title":"Nucleic Acids Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1038\/nchembio.416","article-title":"Replication-dependent instability at (CTG) x (CAG) repeat hairpins in human cells","volume":"6","author":"Liu","year":"2010","journal-title":"Nat. Chem. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"93","DOI":"10.4161\/rna.4.2.5039","article-title":"Secondary structure and dynamics of the r(CGG) repeat in the mRNA of the fragile X mental retardation 1 (FMR1) gene","volume":"4","author":"Zumwalt","year":"2007","journal-title":"RNA Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"6243","DOI":"10.1093\/nar\/gkg818","article-title":"The fragile X syndrome repeats form RNA hairpins that do not activate the interferon-inducible protein kinase, PKR, but are cut by Dicer","volume":"31","author":"Handa","year":"2003","journal-title":"Nucleic Acids Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"5469","DOI":"10.1093\/nar\/gkg766","article-title":"RNA structure of trinucleotide repeats associated with human neurological diseases","volume":"31","author":"Sobczak","year":"2003","journal-title":"Nucleic Acids Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"4145","DOI":"10.1093\/nar\/gkh745","article-title":"Destabilization of tetraplex structures of the fragile X repeat sequence (CGG)n is mediated by homolog-conserved domains in three members of the hnRNP family","volume":"32","author":"Khateb","year":"2004","journal-title":"Nucleic Acids Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"5775","DOI":"10.1093\/nar\/gkm636","article-title":"The tetraplex (CGG)n destabilizing proteins hnRNP A2 and CBF-A enhance the in vivo translation of fragile X premutation mRNA","volume":"35","author":"Khateb","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3672","DOI":"10.1093\/nar\/gkf506","article-title":"Distinct domains in the CArG-box binding factor A destabilize tetraplex forms of the fragile X expanded sequence d(CGG)n","volume":"30","author":"Cohen","year":"2002","journal-title":"Nucleic Acids Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3963","DOI":"10.1093\/nar\/gkg453","article-title":"The cationic porphyrin TMPyP4 destabilizes the tetraplex form of the fragile X syndrome expanded sequence d(CGG)n","volume":"31","author":"Cohen","year":"2003","journal-title":"Nucleic Acids Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1006\/jmbi.1995.0644","article-title":"Solution structure of a DNA quadruplex containing the fragile X syndrome triplet repeat","volume":"254","author":"Kettani","year":"1995","journal-title":"J. Mol. Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"10196","DOI":"10.1093\/nar\/gku710","article-title":"Distinctive structural motifs of RNA G-quadruplexes composed of AGG, CGG and UGG trinucleotide repeats","volume":"42","author":"Malgowska","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1656","DOI":"10.1002\/cbic.201900696","article-title":"Structure Validation of G-Rich RNAs in Noncoding Regions of the Human Genome","volume":"21","author":"Binas","year":"2020","journal-title":"ChemBioChem"},{"doi-asserted-by":"crossref","unstructured":"Asamitsu, S., Yabuki, Y., Ikenoshita, S., Kawakubo, K., Kawasaki, M., Usuki, S., Nakayama, Y., Adachi, K., Kugoh, H., and Ishii, K. (2021). CGG repeat RNA G-quadruplexes interact with FMRpolyG to cause neuronal dysfunction in fragile X-related tremor\/ataxia syndrome. Sci. Adv., 7.","key":"ref_45","DOI":"10.1126\/sciadv.abd9440"},{"doi-asserted-by":"crossref","unstructured":"Chen, Y.W., Satange, R., Wu, P.C., Jhan, C.R., Chang, C.K., Chung, K.R., Waring, M.J., Lin, S.W., Hsieh, L.C., and Hou, M.H. (2018). Co(II)(Chromomycin)(2) Complex Induces a Conformational Change of CCG Repeats from i-Motif to Base-Extruded DNA Duplex. Int. J. Mol. Sci., 19.","key":"ref_46","DOI":"10.3390\/ijms19092796"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1021\/ja409515v","article-title":"Base-pairing energies of proton-bound heterodimers of cytosine and modified cytosines: Implications for the stability of DNA i-motif conformations","volume":"136","author":"Yang","year":"2014","journal-title":"J. Am. Chem. Soc."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"4684","DOI":"10.1093\/nar\/29.22.4684","article-title":"The fragile X chromosome (GCC) repeat folds into a DNA tetraplex at neutral pH","volume":"29","author":"Fojtik","year":"2001","journal-title":"Nucleic Acids Res."},{"doi-asserted-by":"crossref","unstructured":"Loomis, E.W., Sanz, L.A., Chedin, F., and Hagerman, P.J. (2014). Transcription-associated R-loop formation across the human FMR1 CGG-repeat region. PLoS Genet., 10.","key":"ref_49","DOI":"10.1371\/journal.pgen.1004294"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3689","DOI":"10.1093\/hmg\/ddw215","article-title":"Sustained expression of FMR1 mRNA from reactivated fragile X syndrome alleles after treatment with small molecules that prevent trimethylation of H3K27","volume":"25","author":"Kumari","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1534\/genetics.118.301672","article-title":"The G-rich Repeats in FMR1 and C9orf72 Loci Are Hotspots for Local Unpairing of DNA","volume":"210","author":"Cohen","year":"2018","journal-title":"Genetics"},{"doi-asserted-by":"crossref","unstructured":"Groh, M., Lufino, M.M., Wade-Martins, R., and Gromak, N. (2014). R-loops associated with triplet repeat expansions promote gene silencing in Friedreich ataxia and fragile X syndrome. PLoS Genet., 10.","key":"ref_52","DOI":"10.1371\/journal.pgen.1004318"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1590","DOI":"10.1101\/gr.158436.113","article-title":"GC skew at the 5\u2032 and 3\u2032 ends of human genes links R-loop formation to epigenetic regulation and transcription termination","volume":"23","author":"Ginno","year":"2013","journal-title":"Genome Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1073\/pnas.1810409116","article-title":"DNA damage and genome instability by G-quadruplex ligands are mediated by R loops in human cancer cells","volume":"116","author":"Manzo","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.1093\/nar\/gkq935","article-title":"Determinants of R-loop formation at convergent bidirectionally transcribed trinucleotide repeats","volume":"39","author":"Reddy","year":"2011","journal-title":"Nucleic Acids Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1002\/bip.21555","article-title":"CGG repeats associated with fragile X chromosome form left-handed Z-DNA structure","volume":"95","author":"Renciuk","year":"2011","journal-title":"Biopolymers"},{"unstructured":"Genetic Modifiers of Huntington\u2019s Disease Consortium (2015). Identification of Genetic Factors that Modify Clinical Onset of Huntington\u2019s Disease. Cell, 162, 516\u2013526.","key":"ref_57"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1016\/S1474-4422(17)30161-8","article-title":"Identification of genetic variants associated with Huntington\u2019s disease progression: A genome-wide association study","volume":"16","author":"Moss","year":"2017","journal-title":"Lancet Neurol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"3859","DOI":"10.1093\/hmg\/ddx286","article-title":"A modifier of Huntington\u2019s disease onset at the MLH1 locus","volume":"26","author":"Lee","year":"2017","journal-title":"Hum. Mol. Genet."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1002\/ana.24656","article-title":"DNA repair pathways underlie a common genetic mechanism modulating onset in polyglutamine diseases","volume":"79","author":"Bettencourt","year":"2016","journal-title":"Ann. Neurol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1093\/hmg\/ddy375","article-title":"FAN1 modifies Huntington\u2019s disease progression by stabilizing the expanded HTT CAG repeat","volume":"28","author":"Goold","year":"2019","journal-title":"Hum. Mol. Genet."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.dnarep.2016.01.001","article-title":"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","volume":"40","author":"Morales","year":"2016","journal-title":"DNA Repair (Amst)"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"R83","DOI":"10.1093\/hmg\/ddx261","article-title":"Genetic modifiers of Mendelian disease: Huntington\u2019s disease and the trinucleotide repeat disorders","volume":"26","author":"Holmans","year":"2017","journal-title":"Hum. Mol. Genet."},{"doi-asserted-by":"crossref","unstructured":"Zhao, X.N., Lokanga, R., Allette, K., Gazy, I., Wu, D., and Usdin, K. (2016). A MutSbeta-Dependent Contribution of MutSalpha to Repeat Expansions in Fragile X Premutation Mice?. PLoS Genet., 12.","key":"ref_64","DOI":"10.1371\/journal.pgen.1006190"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"149","DOI":"10.3233\/JHD-200423","article-title":"Modifiers of Somatic Repeat Instability in Mouse Models of Friedreich Ataxia and the Fragile X-Related Disorders: Implications for the Mechanism of Somatic Expansion in Huntington\u2019s Disease","volume":"10","author":"Zhao","year":"2021","journal-title":"J. Huntingt. Dis."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"123","DOI":"10.3233\/JHD-200426","article-title":"Modifiers of CAG\/CTG Repeat Instability: Insights from Mammalian Models","volume":"10","author":"Wheeler","year":"2021","journal-title":"J. Huntingt. Dis."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1038\/nsmb965","article-title":"(CAG)(n)-hairpin DNA binds to Msh2-Msh3 and changes properties of mismatch recognition","volume":"12","author":"Owen","year":"2005","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1093\/hmg\/ddm054","article-title":"Triplet repeat mutation length gains correlate with cell-type specific vulnerability in Huntington disease brain","volume":"16","author":"Shelbourne","year":"2007","journal-title":"Hum. Mol. Genet."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"509","DOI":"10.18632\/aging.100324","article-title":"Cockayne syndrome B protein antagonizes OGG1 in modulating CAG repeat length in vivo","volume":"3","author":"Kovtun","year":"2011","journal-title":"Aging"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"6655","DOI":"10.1021\/bi9007403","article-title":"Structure-dependent DNA damage and repair in a trinucleotide repeat sequence","volume":"48","author":"Jarem","year":"2009","journal-title":"Biochemistry"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"4939","DOI":"10.1093\/hmg\/dds337","article-title":"Neil1 is a genetic modifier of somatic and germline CAG trinucleotide repeat instability in R6\/1 mice","volume":"21","author":"Mollersen","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.gene.2007.02.026","article-title":"Regional FMRP deficits and large repeat expansions into the full mutation range in a new Fragile X premutation mouse model","volume":"395","author":"Entezam","year":"2007","journal-title":"Gene"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.1016\/j.scr.2013.08.010","article-title":"Oxidative stress causes DNA triplet expansion in Huntington\u2019s disease mouse embryonic stem cells","volume":"11","author":"Jonson","year":"2013","journal-title":"Stem Cell Res."},{"doi-asserted-by":"crossref","unstructured":"Budworth, H., Harris, F.R., Williams, P., Lee, D.Y., Holt, A., Pahnke, J., Szczesny, B., Acevedo-Torres, K., Ayala-Pena, S., and McMurray, C.T. (2015). Suppression of Somatic Expansion Delays the Onset of Pathophysiology in a Mouse Model of Huntington\u2019s Disease. PLoS Genet., 11.","key":"ref_74","DOI":"10.1371\/journal.pgen.1005267"},{"doi-asserted-by":"crossref","unstructured":"Mollersen, L., Moldestad, O., Rowe, A.D., Bjolgerud, A., Holm, I., Tveteras, L., Klungland, A., and Retterstol, L. (2016). Effects of Anthocyanins on CAG Repeat Instability and Behaviour in Huntington\u2019s Disease R6\/1 Mice. PLoS Curr., 8.","key":"ref_75","DOI":"10.1371\/currents.hd.58d04209ab6d5de0844db7ef5628ff67"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"4985","DOI":"10.1093\/hmg\/ddu213","article-title":"X inactivation plays a major role in the gender bias in somatic expansion in a mouse model of the fragile X-related disorders: Implications for the mechanism of repeat expansion","volume":"23","author":"Lokanga","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1038\/nature05778","article-title":"OGG1 initiates age-dependent CAG trinucleotide expansion in somatic cells","volume":"447","author":"Kovtun","year":"2007","journal-title":"Nature"},{"doi-asserted-by":"crossref","unstructured":"Lokanga, R.A., Senejani, A.G., Sweasy, J.B., and Usdin, K. (2015). Heterozygosity for a hypomorphic Polbeta mutation reduces the expansion frequency in a mouse model of the Fragile X-related disorders. PLoS Genet., 11.","key":"ref_78","DOI":"10.1371\/journal.pgen.1005181"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1002\/humu.22464","article-title":"The mismatch repair protein MSH2 is rate limiting for repeat expansion in a fragile X premutation mouse model","volume":"35","author":"Lokanga","year":"2014","journal-title":"Hum. Mutat."},{"doi-asserted-by":"crossref","unstructured":"Miller, C.J., Kim, G.Y., Zhao, X., and Usdin, K. (2020). All three mammalian MutL complexes are required for repeat expansion in a mouse cell model of the Fragile X-related disorders. PLoS Genet, 16.","key":"ref_80","DOI":"10.1371\/journal.pgen.1008902"},{"doi-asserted-by":"crossref","unstructured":"Zhao, X., Zhang, Y., Wilkins, K., Edelmann, W., and Usdin, K. (2018). MutLgamma promotes repeat expansion in a Fragile X mouse model while EXO1 is protective. PLoS Genet., 14.","key":"ref_81","DOI":"10.1371\/journal.pgen.1007719"},{"key":"ref_82","first-page":"7087","article-title":"Mutsbeta generates both expansions and contractions in a mouse model of the Fragile X-associated disorders","volume":"24","author":"Zhao","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.dnarep.2018.12.004","article-title":"Double-strand break repair plays a role in repeat instability in a fragile X mouse model","volume":"74","author":"Gazy","year":"2019","journal-title":"DNA Repair (Amst)"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1016\/j.celrep.2013.02.004","article-title":"Sequestration of DROSHA and DGCR8 by expanded CGG RNA repeats alters microRNA processing in fragile X-associated tremor\/ataxia syndrome","volume":"3","author":"Sellier","year":"2013","journal-title":"Cell Rep."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1016\/j.neuron.2013.03.026","article-title":"CGG repeat-associated translation mediates neurodegeneration in fragile X tremor ataxia syndrome","volume":"78","author":"Todd","year":"2013","journal-title":"Neuron"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"4317","DOI":"10.1093\/hmg\/ddv165","article-title":"RAN translation at CGG repeats induces ubiquitin proteasome system impairment in models of fragile X-associated tremor ataxia syndrome","volume":"24","author":"Oh","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1146\/annurev-neuro-070918-050405","article-title":"Repeat-Associated Non-ATG Translation: Molecular Mechanisms and Contribution to Neurological Disease","volume":"42","author":"Nguyen","year":"2019","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1016\/j.molcel.2018.12.016","article-title":"R-Loops Enhance Polycomb Repression at a Subset of Developmental Regulator Genes","volume":"73","author":"Warburton","year":"2019","journal-title":"Mol. Cell"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1038\/nature13787","article-title":"R-loops induce repressive chromatin marks over mammalian gene terminators","volume":"516","author":"Proudfoot","year":"2014","journal-title":"Nature"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"16527","DOI":"10.1073\/pnas.1921219117","article-title":"Folate stress induces SLX1- and RAD51-dependent mitotic DNA synthesis at the fragile X locus in human cells","volume":"117","author":"Garribba","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"7856","DOI":"10.1093\/nar\/gkaa573","article-title":"A point mutation in the nuclease domain of MLH3 eliminates repeat expansions in a mouse stem cell model of the Fragile X-related disorders","volume":"48","author":"Hayward","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"3535","DOI":"10.1073\/pnas.1914718117","article-title":"Human MutLgamma, the MLH1-MLH3 heterodimer, is an endonuclease that promotes DNA expansion","volume":"117","author":"Kadyrova","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"2702","DOI":"10.1016\/j.febslet.2005.04.004","article-title":"Long CGG-repeat tracts are toxic to human cells: Implications for carriers of Fragile X premutation alleles","volume":"579","author":"Handa","year":"2005","journal-title":"FEBS Lett."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1016\/S0896-6273(03)00533-6","article-title":"RNA-mediated neurodegeneration caused by the fragile X premutation rCGG repeats in Drosophila","volume":"39","author":"Jin","year":"2003","journal-title":"Neuron"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1093\/hmg\/ddg114","article-title":"The FMR1 CGG repeat mouse displays ubiquitin-positive intranuclear neuronal inclusions; implications for the cerebellar tremor\/ataxia syndrome","volume":"12","author":"Willemsen","year":"2003","journal-title":"Hum. Mol. Genet."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"2443","DOI":"10.1093\/hmg\/ddp182","article-title":"Ectopic expression of CGG containing mRNA is neurotoxic in mammals","volume":"18","author":"Hashem","year":"2009","journal-title":"Hum. Mol. Genet."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"2161","DOI":"10.1093\/hmg\/ddr101","article-title":"CGG-repeat length threshold for FMR1 RNA pathogenesis in a cellular model for FXTAS","volume":"20","author":"Hoem","year":"2011","journal-title":"Hum. Mol. Genet."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1760","DOI":"10.1093\/brain\/awf184","article-title":"Neuronal intranuclear inclusions in a new cerebellar tremor\/ataxia syndrome among fragile X carriers","volume":"125","author":"Greco","year":"2002","journal-title":"Brain"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"103","DOI":"10.4161\/rna.1.2.1035","article-title":"FMR1 RNA within the intranuclear inclusions of fragile X-associated tremor\/ataxia syndrome (FXTAS)","volume":"1","author":"Tassone","year":"2004","journal-title":"RNA Biol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"13938","DOI":"10.1073\/pnas.1305426110","article-title":"R-loop formation at Snord116 mediates topotecan inhibition of Ube3a-antisense and allele-specific chromatin decondensation","volume":"110","author":"Powell","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1016\/j.molcel.2012.01.017","article-title":"R-loop formation is a distinctive characteristic of unmethylated human CpG island promoters","volume":"45","author":"Ginno","year":"2012","journal-title":"Mol. Cell"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1038\/s41588-018-0306-6","article-title":"GADD45A binds R-loops and recruits TET1 to CpG island promoters","volume":"51","author":"Arab","year":"2019","journal-title":"Nat. Genet."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1021\/acs.chemrestox.8b00332","article-title":"Oxidative Modification of the Potential G-Quadruplex Sequence in the PCNA Gene Promoter Can Turn on Transcription","volume":"32","author":"Redstone","year":"2019","journal-title":"Chem. Res. Toxicol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1038\/emboj.2010.21","article-title":"Sam68 sequestration and partial loss of function are associated with splicing alterations in FXTAS patients","volume":"29","author":"Sellier","year":"2010","journal-title":"EMBO J."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.molcel.2016.02.034","article-title":"CGG Repeat-Associated Non-AUG Translation Utilizes a Cap-Dependent Scanning Mechanism of Initiation to Produce Toxic Proteins","volume":"62","author":"Kearse","year":"2016","journal-title":"Mol. Cell"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1002\/ana.24800","article-title":"Repeat-associated non-AUG translation from antisense CCG repeats in fragile X tremor\/ataxia syndrome","volume":"80","author":"Krans","year":"2016","journal-title":"Ann. Neurol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.neuron.2016.12.016","article-title":"Translation of Expanded CGG Repeats into FMRpolyG Is Pathogenic and May Contribute to Fragile X Tremor Ataxia Syndrome","volume":"93","author":"Sellier","year":"2017","journal-title":"Neuron"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"2828","DOI":"10.1093\/nar\/18.9.2828","article-title":"Evaluation of the fidelity of initiation of translation in reticulocyte lysates from commercial sources","volume":"18","author":"Kozak","year":"1990","journal-title":"Nucleic Acids Res."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1186\/s40478-019-0782-7","article-title":"Neuropathology of RAN translation proteins in fragile X-associated tremor\/ataxia syndrome","volume":"7","author":"Krans","year":"2019","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"e01954","DOI":"10.1016\/j.heliyon.2019.e01954","article-title":"Intracellular FMRpolyG-Hsp70 complex in fibroblast cells from a patient affected by fragile X tremor ataxia syndrome","volume":"5","author":"Bonapace","year":"2019","journal-title":"Heliyon"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1186\/s40478-014-0162-2","article-title":"FMRpolyG-positive inclusions in CNS and non-CNS organs of a fragile X premutation carrier with fragile X-associated tremor\/ataxia syndrome","volume":"2","author":"Buijsen","year":"2014","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/s13048-020-00623-w","article-title":"FMRpolyG accumulates in FMR1 premutation granulosa cells","volume":"13","author":"Elizur","year":"2020","journal-title":"J. Ovarian Res."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1017\/S1355838200991544","article-title":"Expanded CUG repeat RNAs form hairpins that activate the double-stranded RNA-dependent protein kinase PKR","volume":"6","author":"Tian","year":"2000","journal-title":"RNA"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"18591","DOI":"10.1073\/pnas.2005748117","article-title":"Metformin inhibits RAN translation through PKR pathway and mitigates disease in C9orf72 ALS\/FTD mice","volume":"117","author":"Zu","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"2005","DOI":"10.1038\/s41467-017-02200-0","article-title":"RAN translation at C9orf72-associated repeat expansions is selectively enhanced by the integrated stress response","volume":"8","author":"Green","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"599101","DOI":"10.3389\/fmolb.2020.599101","article-title":"Lack of a Clear Behavioral Phenotype in an Inducible FXTAS Mouse Model Despite the Presence of Neuronal FMRpolyG-Positive Aggregates","volume":"7","author":"Haify","year":"2020","journal-title":"Front. Mol. Biosci."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"600840","DOI":"10.3389\/fmolb.2020.600840","article-title":"Human Cerebral Cortex Proteome of Fragile X-Associated Tremor\/Ataxia Syndrome","volume":"7","author":"Holm","year":"2020","journal-title":"Front. Mol. Biosci."},{"doi-asserted-by":"crossref","unstructured":"Rodriguez, S., Sahin, A., Schrank, B.R., Al-Lawati, H., Costantino, I., Benz, E., Fard, D., Albers, A.D., Cao, L., and Gomez, A.C. (2021). Genome-encoded cytoplasmic double-stranded RNAs, found in C9ORF72 ALS-FTD brain, propagate neuronal loss. Sci. Transl. Med., 13.","key":"ref_118","DOI":"10.1126\/scitranslmed.aaz4699"},{"doi-asserted-by":"crossref","unstructured":"Cabal-Herrera, A.M., Tassanakijpanich, N., Salcedo-Arellano, M.J., and Hagerman, R.J. (2020). Fragile X-Associated Tremor\/Ataxia Syndrome (FXTAS): Pathophysiology and Clinical Implications. Int. J. Mol. Sci., 21.","key":"ref_119","DOI":"10.3390\/ijms21124391"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"3167","DOI":"10.1016\/j.celrep.2019.08.041","article-title":"Dual Processing of R-Loops and Topoisomerase I Induces Transcription-Dependent DNA Double-Strand Breaks","volume":"28","author":"Cristini","year":"2019","journal-title":"Cell Rep."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1016\/j.molcel.2019.01.024","article-title":"R-Loops as Cellular Regulators and Genomic Threats","volume":"73","author":"Crossley","year":"2019","journal-title":"Mol. Cell"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"1482","DOI":"10.1017\/S1355838202020642","article-title":"Reduced FMR1 mRNA translation efficiency in fragile X patients with premutations","volume":"8","author":"Primerano","year":"2002","journal-title":"RNA"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1038\/s41398-020-00863-w","article-title":"Elevated FMR1-mRNA and lowered FMRP-A double-hit mechanism for psychiatric features in men with FMR1 premutations","volume":"10","author":"Schneider","year":"2020","journal-title":"Transl. Psychiatry"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1126\/science.7732383","article-title":"Translational suppression by trinucleotide repeat expansion at FMR1","volume":"268","author":"Feng","year":"1995","journal-title":"Science"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"6575","DOI":"10.1093\/hmg\/ddu378","article-title":"Polycomb group complexes are recruited to reactivated FMR1 alleles in Fragile X syndrome in response to FMR1 transcription","volume":"23","author":"Kumari","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1038\/s41467-020-15609-x","article-title":"RNA-DNA strand exchange by the Drosophila Polycomb complex PRC2","volume":"11","author":"Alecki","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1016\/j.molcel.2017.02.003","article-title":"Targeting of Polycomb Repressive Complex 2 to RNA by Short Repeats of Consecutive Guanines","volume":"65","author":"Wang","year":"2017","journal-title":"Mol. Cell"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"8295","DOI":"10.1073\/pnas.1819029116","article-title":"Histone H3 tail binds a unique sensing pocket in EZH2 to activate the PRC2 methyltransferase","volume":"116","author":"Jani","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"7983","DOI":"10.1074\/jbc.M110.194027","article-title":"H3K36 methylation antagonizes PRC2-mediated H3K27 methylation","volume":"286","author":"Yuan","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1016\/j.molcel.2011.03.025","article-title":"Histone methylation by PRC2 is inhibited by active chromatin marks","volume":"42","author":"Schmitges","year":"2011","journal-title":"Mol. Cell"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1016\/j.molcel.2003.08.010","article-title":"Cotranscriptionally formed DNA:RNA hybrids mediate transcription elongation impairment and transcription-associated recombination","volume":"12","author":"Huertas","year":"2003","journal-title":"Mol. Cell"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1016\/j.cell.2010.04.038","article-title":"ATM-dependent chromatin changes silence transcription in cis to DNA double-strand breaks","volume":"141","author":"Shanbhag","year":"2010","journal-title":"Cell"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1038\/nsmb.2224","article-title":"DNAPKcs-dependent arrest of RNA polymerase II transcription in the presence of DNA breaks","volume":"19","author":"Pankotai","year":"2012","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/s13229-016-0105-9","article-title":"CGG-repeat dynamics and FMR1 gene silencing in fragile X syndrome stem cells and stem cell-derived neurons","volume":"7","author":"Zhou","year":"2016","journal-title":"Mol. Autism"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1038\/s41580-019-0206-3","article-title":"Regulatory R-loops as facilitators of gene expression and genome stability","volume":"21","author":"Niehrs","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1387\/ijdb.170022hc","article-title":"Epigenetic mechanism of FMR1 inactivation in Fragile X syndrome","volume":"61","author":"Hecht","year":"2017","journal-title":"Int. J. Dev. Biol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"3174","DOI":"10.1093\/hmg\/ddm293","article-title":"An antisense transcript spanning the CGG repeat region of FMR1 is upregulated in premutation carriers but silenced in full mutation individuals","volume":"16","author":"Ladd","year":"2007","journal-title":"Hum. Mol. Genet."},{"doi-asserted-by":"crossref","unstructured":"Kumari, D., Sciascia, N., and Usdin, K. (2020). Small Molecules Targeting H3K9 Methylation Prevent Silencing of Reactivated FMR1 Alleles in Fragile X Syndrome Patient Derived Cells. Genes, 11.","key":"ref_138","DOI":"10.3390\/genes11040356"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.bbagrm.2007.10.005","article-title":"Human chromosome fragility","volume":"1779","author":"Lukusa","year":"2008","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1007\/BF00289445","article-title":"Heritable fragile sites on human chromosomes. III. Detection of fra(X)(q27) in males with X-linked mental retardation and in their female relatives","volume":"53","author":"Sutherland","year":"1979","journal-title":"Hum. Genet."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1038\/nsmb.1527","article-title":"Replisome stalling and stabilization at CGG repeats, which are responsible for chromosomal fragility","volume":"16","author":"Voineagu","year":"2009","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.molcel.2013.10.029","article-title":"The DNA replication program is altered at the FMR1 locus in fragile X embryonic stem cells","volume":"53","author":"Gerhardt","year":"2014","journal-title":"Mol. Cell"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1038\/s41467-021-21021-w","article-title":"Short antisense oligonucleotides alleviate the pleiotropic toxicity of RNA harboring expanded CGG repeats","volume":"12","author":"Derbis","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"1711","DOI":"10.1021\/cb300135h","article-title":"A small molecule that targets r(CGG)(exp) and improves defects in fragile X-associated tremor ataxia syndrome","volume":"7","author":"Disney","year":"2012","journal-title":"ACS Chem. Biol."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"295","DOI":"10.3389\/fnins.2020.00295","article-title":"Curcumin Regulates the r(CGG)(exp) RNA Hairpin Structure and Ameliorate Defects in Fragile X-Associated Tremor Ataxia Syndrome","volume":"14","author":"Verma","year":"2020","journal-title":"Front. Neurosci."},{"doi-asserted-by":"crossref","unstructured":"Haify, S.N., Buijsen, R.A.M., Verwegen, L., Severijnen, L., de Boer, H., Boumeester, V., Monshouwer, R., Yang, W.Y., Cameron, M.D., and Willemsen, R. (2021). Small molecule 1a reduces FMRpolyG-mediated toxicity in in vitro and in vivo models for FMR1 premutation. Hum. Mol. Genet.","key":"ref_146","DOI":"10.1093\/hmg\/ddab143"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/17\/9167\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:51:25Z","timestamp":1760165485000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/17\/9167"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,25]]},"references-count":146,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2021,9]]}},"alternative-id":["ijms22179167"],"URL":"https:\/\/doi.org\/10.3390\/ijms22179167","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2021,8,25]]}}}