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  • 标题:Linker domain function predicts pathogenic MLH1 missense variants
  • 本地全文:下载
  • 作者:James London ; Juana Martín-López ; Inho Yang
  • 期刊名称:Proceedings of the National Academy of Sciences
  • 印刷版ISSN:0027-8424
  • 电子版ISSN:1091-6490
  • 出版年度:2021
  • 卷号:118
  • 期号:9
  • 页码:1
  • DOI:10.1073/pnas.2019215118
  • 出版社:The National Academy of Sciences of the United States of America
  • 摘要:The pathogenic consequences of 369 unique human HsMLH1 missense variants has been hampered by the lack of a detailed function in mismatch repair (MMR). Here single-molecule images show that HsMSH2-HsMSH6 provides a platform for HsMLH1-HsPMS2 to form a stable sliding clamp on mismatched DNA. The mechanics of sliding clamp progression solves a significant operational puzzle in MMR and provides explicit predictions for the distribution of clinically relevant HsMLH1 missense mutations.
  • 关键词:mismatch repair ; Lynch syndrome ; HNPCC ; single molecule ; sliding clamp
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