{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Lang WH"],"funding":["NINDS NIH HHS","NCI NIH HHS","NIGMS NIH HHS"],"pagination":["E837-44"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC3198364"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["108(42)"],"pubmed_abstract":["Insertion and deletion of small heteroduplex loops are common mutations in DNA, but why some loops are prone to mutation and others are efficiently repaired is unknown. Here we report that the mismatch recognition complex, MSH2/MSH3, discriminates between a repair-competent and a repair-resistant loop by sensing the conformational dynamics of their junctions. MSH2/MSH3 binds, bends, and dissociates from repair-competent loops to signal downstream repair. Repair-resistant Cytosine-Adenine-Guanine (CAG) loops adopt a unique DNA junction that traps nucleotide-bound MSH2/MSH3, and inhibits its dissociation from the DNA. We envision that junction dynamics is an active participant and a conformational regulator of repair signaling, and governs whether a loop is removed by MSH2/MSH3 or escapes to become a precursor for mutation."],"journal":["Proceedings of the National Academy of Sciences of the United States of America"],"pubmed_title":["Conformational trapping of mismatch recognition complex MSH2/MSH3 on repair-resistant DNA loops."],"pmcid":["PMC3198364"],"funding_grant_id":["NS40738","CA092584","NS062384","GM066359","R01 NS040738","R01 NS060115","R01 GM066359","NS060115","R01 NS062384","P01 CA092584"],"pubmed_authors":["Hura GL","McMurray CT","Coats JE","Lin Y","Majka J","Rasnik I","Lang WH"],"additional_accession":[]},"is_claimable":false,"name":"Conformational trapping of mismatch recognition complex MSH2/MSH3 on repair-resistant DNA loops.","description":"Insertion and deletion of small heteroduplex loops are common mutations in DNA, but why some loops are prone to mutation and others are efficiently repaired is unknown. Here we report that the mismatch recognition complex, MSH2/MSH3, discriminates between a repair-competent and a repair-resistant loop by sensing the conformational dynamics of their junctions. MSH2/MSH3 binds, bends, and dissociates from repair-competent loops to signal downstream repair. Repair-resistant Cytosine-Adenine-Guanine (CAG) loops adopt a unique DNA junction that traps nucleotide-bound MSH2/MSH3, and inhibits its dissociation from the DNA. We envision that junction dynamics is an active participant and a conformational regulator of repair signaling, and governs whether a loop is removed by MSH2/MSH3 or escapes to become a precursor for mutation.","dates":{"release":"2011-01-01T00:00:00Z","publication":"2011 Oct","modification":"2021-02-21T02:08:38Z","creation":"2019-03-27T00:45:15Z"},"accession":"S-EPMC3198364","cross_references":{"pubmed":["21960445"],"doi":["10.1073/pnas.1105461108"]}}