ATP-dependent interaction of human mismatch repair proteins and dual role of PCNA in mismatch repair

Liya Gu, Yu Hong, Scott McCulloch, Hiroyuki Watanabe, Guo Min Li

Research output: Contribution to journalArticle

177 Scopus citations

Abstract

DNA mismatch repair ensures genomic stability by correcting biosynthetic errors and by blocking homologous recombination. MutS-like and MutL-like proteins play important roles in these processes. In Escherichia coli and yeast these two types of proteins form a repair initiation complex that binds to mismatched DNA. However, whether human MutS and MutL homologs interact to form a complex has not been elucidated. Using immunoprecipitation and Western blot analysis we show here that human MSH2, MLH1, PMS2 and proliferating cell nuclear antigen (PCNA) can be co-immunoprecipitated, suggesting formation of a repair initiation complex among these proteins. Formation of the initiation complex is dependent on ATP hydrolysis and at least functional MSH2 and MLH1 proteins, because the complex could not be detected in tumor cells that produce truncated MLH1 or MSH2 protein. We also demonstrate that PCNA is required in human mismatch repair not only at the step of repair initiation, but also at the step of repair DNA re-synthesis.

Original languageEnglish (US)
Pages (from-to)1173-1178
Number of pages6
JournalNucleic acids research
Volume26
Issue number5
DOIs
StatePublished - Mar 1 1998

ASJC Scopus subject areas

  • Genetics

Fingerprint Dive into the research topics of 'ATP-dependent interaction of human mismatch repair proteins and dual role of PCNA in mismatch repair'. Together they form a unique fingerprint.

  • Cite this