{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:24:46Z","timestamp":1790774686162,"version":"4.1.0"},"reference-count":58,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2014,6,27]],"date-time":"2014-06-27T00:00:00Z","timestamp":1403827200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0100523","type":"journal-article","created":{"date-parts":[[2014,6,27]],"date-time":"2014-06-27T20:23:28Z","timestamp":1403900608000},"page":"e100523","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":26,"title":["MutL\u03b1 Heterodimers Modify the Molecular Phenotype of Friedreich Ataxia"],"prefix":"10.1371","volume":"9","author":[{"given":"Vahid","family":"Ezzatizadeh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiranjeevi","family":"Sandi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madhavi","family":"Sandi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Anjomani-Virmouni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sahar","family":"Al-Mahdawi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark A.","family":"Pook","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2014,6,27]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1126\/science.271.5254.1423","article-title":"Friedreich&apos;s ataxia: autosomal recessive disease caused by an intronic GAA triplet repeat expansion","volume":"271","author":"V Campuzano","year":"1996","journal-title":"Science"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1038\/nature01596","article-title":"DNA triplet repeats mediate heterochromatin-protein-1-sensitive variegated gene silencing","volume":"422","author":"A Saveliev","year":"2003","journal-title":"Nature"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"1625","DOI":"10.1096\/fj.07-097857","article-title":"DNA triplexes and Friedreich ataxia","volume":"22","author":"RD Wells","year":"2008","journal-title":"FASEB J"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"5351","DOI":"10.1093\/nar\/gkm589","article-title":"A persistent RNA.DNA hybrid formed by transcription of the Friedreich ataxia triplet repeat in live bacteria, and by T7 RNAP in vitro","volume":"35","author":"E Grabczyk","year":"2007","journal-title":"Nucleic Acids Res"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"1771","DOI":"10.1093\/hmg\/6.11.1771","article-title":"Frataxin is reduced in Friedreich ataxia patients and is associated with mitochondrial membranes","volume":"6","author":"V Campuzano","year":"1997","journal-title":"Hum Mol Genet"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1093\/hmg\/9.2.275","article-title":"Clinical, biochemical and molecular genetic correlations in Friedreich&apos;s ataxia","volume":"9","author":"JL Bradley","year":"2000","journal-title":"Hum Mol Genet"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jns.2011.01.010","article-title":"Friedreich&apos;s ataxia: pathology, pathogenesis, and molecular genetics","volume":"303","author":"AH Koeppen","year":"2011","journal-title":"J Neurol Sci"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1038\/nrneurol.2009.26","article-title":"Diagnosis and treatment of Friedreich ataxia: a European perspective","volume":"5","author":"JB Schulz","year":"2009","journal-title":"Nat Rev Neurol"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/s00415-009-1003-2","article-title":"The pathogenesis of Friedreich ataxia and the structure and function of frataxin","volume":"256 Suppl 1","author":"M Pandolfo","year":"2009","journal-title":"J Neurol"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1007\/978-1-4615-0117-6_5","article-title":"The molecular basis of Friedreich ataxia","volume":"516","author":"M Pandolfo","year":"2002","journal-title":"Adv Exp Med Biol"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1093\/hmg\/6.8.1261","article-title":"The Friedreich ataxia GAA triplet repeat: premutation and normal alleles","volume":"6","author":"L Montermini","year":"1997","journal-title":"Hum Mol Genet"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1002\/ana.21052","article-title":"Progressive GAA expansions in dorsal root ganglia of Friedreich&apos;s ataxia patients","volume":"61","author":"I De Biase","year":"2007","journal-title":"Ann Neurol"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ygeno.2007.04.001","article-title":"Somatic instability of the expanded GAA triplet-repeat sequence in Friedreich ataxia progresses throughout life","volume":"90","author":"I De Biase","year":"2007","journal-title":"Genomics"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"1901","DOI":"10.1093\/hmg\/7.12.1901","article-title":"Parental gender, age at birth and expansion length influence GAA repeat intergenerational instability in the X25 gene: pedigree studies and analysis of sperm from patients with Friedreich&apos;s ataxia","volume":"7","author":"G De Michele","year":"1998","journal-title":"Hum Mol Genet"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1136\/jmg.35.9.713","article-title":"Sperm DNA analysis in a Friedreich ataxia premutation carrier suggests both meiotic and mitotic expansion in the FRDA gene","volume":"35","author":"MB Delatycki","year":"1998","journal-title":"J Med Genet"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1086\/513887","article-title":"Phenotype correlation and intergenerational dynamics of the Friedreich ataxia GAA trinucleotide repeat","volume":"61","author":"E Monros","year":"1997","journal-title":"Am J Hum Genet"},{"key":"ref17","first-page":"460","article-title":"The effect of parental gender on the GAA dynamic mutation in the FRDA gene","volume":"60","author":"L Pianese","year":"1997","journal-title":"Am J Hum Genet"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/j.ygeno.2004.04.003","article-title":"GAA repeat instability in Friedreich ataxia YAC transgenic mice","volume":"84","author":"S Al-Mahdawi","year":"2004","journal-title":"Genomics"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"e74956","DOI":"10.1371\/journal.pone.0074956","article-title":"Friedreich ataxia patient tissues exhibit increased 5-hydroxymethylcytosine modification and decreased CTCF binding at the FXN locus","volume":"8","author":"S Al-Mahdawi","year":"2013","journal-title":"PLoS One"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.nbd.2012.01.002","article-title":"The mismatch repair system protects against intergenerational GAA repeat instability in a Friedreich ataxia mouse model","volume":"46","author":"V Ezzatizadeh","year":"2012","journal-title":"Neurobiol Dis"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"2855","DOI":"10.1093\/hmg\/dds110","article-title":"Interferon gamma upregulates frataxin and corrects the functional deficits in a Friedreich ataxia model","volume":"21","author":"B Tomassini","year":"2012","journal-title":"Hum Mol Genet"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1016\/j.nbd.2011.02.016","article-title":"Prolonged treatment with pimelic o-aminobenzamide HDAC inhibitors ameliorates the disease phenotype of a Friedreich ataxia mouse model","volume":"42","author":"C Sandi","year":"2011","journal-title":"Neurobiol Dis"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1093\/hmg\/ddm346","article-title":"The Friedreich ataxia GAA repeat expansion mutation induces comparable epigenetic changes in human and transgenic mouse brain and heart tissues","volume":"17","author":"S Al-Mahdawi","year":"2008","journal-title":"Hum Mol Genet"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1016\/j.ygeno.2006.06.015","article-title":"GAA repeat expansion mutation mouse models of Friedreich ataxia exhibit oxidative stress leading to progressive neuronal and cardiac pathology","volume":"88","author":"S Al-Mahdawi","year":"2006","journal-title":"Genomics"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1007\/s00439-006-0249-3","article-title":"The GAA triplet-repeat is unstable in the context of the human FXN locus and displays age-dependent expansions in cerebellum and DRG in a transgenic mouse model","volume":"120","author":"RM Clark","year":"2007","journal-title":"Hum Genet"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1038\/nrm2854","article-title":"Repeat instability as the basis for human diseases and as a potential target for therapy","volume":"11","author":"A Lopez Castel","year":"2010","journal-title":"Nat Rev Mol Cell Biol"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"e47085","DOI":"10.1371\/journal.pone.0047085","article-title":"Pms2 suppresses large expansions of the (GAA.TTC)n sequence in neuronal tissues","volume":"7","author":"RL Bourn","year":"2012","journal-title":"PLoS One"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1038\/cr.2007.115","article-title":"Mechanisms and functions of DNA mismatch repair","volume":"18","author":"GM Li","year":"2008","journal-title":"Cell Res"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"5321","DOI":"10.1093\/nar\/gkh855","article-title":"Human MutL homolog (MLH1) function in DNA mismatch repair: a prospective screen for missense mutations in the ATPase domain","volume":"32","author":"AR Ellison","year":"2004","journal-title":"Nucleic Acids Res"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"e1003930","DOI":"10.1371\/journal.pgen.1003930","article-title":"Mismatch Repair Genes Mlh1 and Mlh3 Modify CAG Instability in Huntington&apos;s Disease Mice: Genome-Wide and Candidate Approaches","volume":"9","author":"RM Pinto","year":"2013","journal-title":"PLoS Genet"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1016\/S0092-8674(00)81312-4","article-title":"Meiotic pachytene arrest in MLH1-deficient mice","volume":"85","author":"W Edelmann","year":"1996","journal-title":"Cell"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/0092-8674(95)90318-6","article-title":"Male mice defective in the DNA mismatch repair gene PMS2 exhibit abnormal chromosome synapsis in meiosis","volume":"82","author":"SM Baker","year":"1995","journal-title":"Cell"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1007\/BF02722955","article-title":"NCM460, a normal human colon mucosal epithelial cell line","volume":"32","author":"MP Moyer","year":"1996","journal-title":"In Vitro Cell Dev Biol Anim"},{"key":"ref34","first-page":"767","article-title":"Defective expression of the DNA mismatch repair protein, MLH1, alters G2-M cell cycle checkpoint arrest following ionizing radiation","volume":"58","author":"TW Davis","year":"1998","journal-title":"Cancer Res"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1373\/clinchem.2008.112797","article-title":"The MIQE guidelines: minimum information for publication of quantitative real-time PCR experiments","volume":"55","author":"SA Bustin","year":"2009","journal-title":"Clin Chem"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1136\/jnnp.2003.028605","article-title":"Real time PCR quantification of frataxin mRNA in the peripheral blood leucocytes of Friedreich ataxia patients and carriers","volume":"75","author":"L Pianese","year":"2004","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1038\/sj.ejhg.5201628","article-title":"Assessing the pathogenicity of MLH1 missense mutations in patients with suspected hereditary nonpolyposis colorectal cancer: correlation with clinical, genetic and functional features","volume":"14","author":"L Belvederesi","year":"2006","journal-title":"Eur J Hum Genet"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"18424","DOI":"10.1074\/jbc.M001140200","article-title":"Steady-state regulation of the human DNA mismatch repair system","volume":"275","author":"DK Chang","year":"2000","journal-title":"J Biol Chem"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1084\/jem.20111531","article-title":"The ATPase activity of MLH1 is required to orchestrate DNA double-strand breaks and end processing during class switch recombination","volume":"209","author":"R Chahwan","year":"2012","journal-title":"J Exp Med"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"39217","DOI":"10.1074\/jbc.M205209200","article-title":"Sticky DNA, a long GAA.GAA.TTC triplex that is formed intramolecularly, in the sequence of intron 1 of the frataxin gene","volume":"277","author":"AA Vetcher","year":"2002","journal-title":"J Biol Chem"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"3964","DOI":"10.1093\/nar\/gks021","article-title":"Effects of Friedreich&apos;s ataxia GAA repeats on DNA replication in mammalian cells","volume":"40","author":"GS Chandok","year":"2012","journal-title":"Nucleic Acids Res"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/S1097-2765(00)80474-8","article-title":"Sticky DNA: self-association properties of long GAA.TTC repeats in R.R.Y triplex structures from Friedreich&apos;s ataxia","volume":"3","author":"N Sakamoto","year":"1999","journal-title":"Mol Cell"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"e1002305","DOI":"10.1371\/journal.pgen.1002305","article-title":"Genome-wide analysis of heteroduplex DNA in mismatch repair-deficient yeast cells reveals novel properties of meiotic recombination pathways","volume":"7","author":"E Martini","year":"2011","journal-title":"PLoS Genet"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"29861","DOI":"10.1074\/jbc.M112.391961","article-title":"Role of mismatch repair enzymes in GAA.TTC triplet-repeat expansion in Friedreich ataxia induced pluripotent stem cells","volume":"287","author":"J Du","year":"2012","journal-title":"J Biol Chem"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"1609","DOI":"10.1111\/j.1742-4658.2006.05190.x","article-title":"DNA mismatch repair system. Classical and fresh roles","volume":"273","author":"SH Jun","year":"2006","journal-title":"FEBS J"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1016\/j.celrep.2014.01.034","article-title":"RTEL1 Inhibits Trinucleotide Repeat Expansions and Fragility","volume":"6","author":"A Frizzell","year":"2014","journal-title":"Cell Rep"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.mad.2008.02.012","article-title":"DNA mismatch repair: molecular mechanism, cancer, and ageing","volume":"129","author":"P Hsieh","year":"2008","journal-title":"Mech Ageing Dev"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"2815","DOI":"10.1093\/nar\/28.14.2815","article-title":"The GAA*TTC triplet repeat expanded in Friedreich&apos;s ataxia impedes transcription elongation by T7 RNA polymerase in a length and supercoil dependent manner","volume":"28","author":"E Grabczyk","year":"2000","journal-title":"Nucleic Acids Res"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1038\/nrm3098","article-title":"Unravelling the means to an end: RNA polymerase II transcription termination","volume":"12","author":"JN Kuehner","year":"2011","journal-title":"Nat Rev Mol Cell Biol"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"e1004318","DOI":"10.1371\/journal.pgen.1004318","article-title":"R-loops Associated with Triplet Repeat Expansions Promote Gene Silencing in Friedreich Ataxia and Fragile X Syndrome","volume":"10","author":"M Groh","year":"2014","journal-title":"PLoS Genet"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"e46807","DOI":"10.1371\/journal.pone.0046807","article-title":"Nucleotide excision repair, mismatch repair, and R-loops modulate convergent transcription-induced cell death and repeat instability","volume":"7","author":"Y Lin","year":"2012","journal-title":"PLoS One"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"250","DOI":"10.2174\/138920209788488544","article-title":"Involvement of nucleotide excision and mismatch repair mechanisms in double strand break repair","volume":"10","author":"Y Zhang","year":"2009","journal-title":"Curr Genomics"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1534\/genetics.106.059840","article-title":"The relative roles of three DNA repair pathways in preventing Caenorhabditis elegans mutation accumulation","volume":"174","author":"DR Denver","year":"2006","journal-title":"Genetics"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1111\/j.1749-0774.2005.tb00001.x","article-title":"Involvement of mismatch repair in transcription-coupled nucleotide excision repair","volume":"18","author":"K Kobayashi","year":"2005","journal-title":"Hum Cell"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1038\/342095a0","article-title":"Induction of the Escherichia coli lactose operon selectively increases repair of its transcribed DNA strand","volume":"342","author":"I Mellon","year":"1989","journal-title":"Nature"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1126\/science.272.5261.557","article-title":"Transcription-coupled repair deficiency and mutations in human mismatch repair genes","volume":"272","author":"I Mellon","year":"1996","journal-title":"Science"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"5856","DOI":"10.1038\/sj.onc.1204721","article-title":"Defects in transcription coupled repair interfere with expression of p90(MDM2) in response to ultraviolet light","volume":"20","author":"J Michalowski","year":"2001","journal-title":"Oncogene"},{"key":"ref58","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.canlet.2005.12.009","article-title":"Overexpression of the DNA mismatch repair factor, PMS2, confers hypermutability and DNA damage tolerance","volume":"244","author":"SL Gibson","year":"2006","journal-title":"Cancer Lett"}],"container-title":["PLoS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0100523","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,5,8]],"date-time":"2020-05-08T21:51:46Z","timestamp":1588974706000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0100523"}},"subtitle":[],"editor":[{"given":"Efthimios M. C.","family":"Skoulakis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2014,6,27]]},"references-count":58,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2014,6,27]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0100523","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,6,27]]}}}