TY - JOUR
T1 - ATP-dependent interaction of human mismatch repair proteins and dual role of PCNA in mismatch repair
AU - Gu, Liya
AU - Hong, Yu
AU - McCulloch, Scott
AU - Watanabe, Hiroyuki
AU - Li, Guo Min
N1 - Funding Information:
We thank Yue Xiong and Henming Ke of the University of North Carolina at Chapel Hill for reagents and discussion during the course of the experiments and for supporting H.W. We thank Paul Modrich and Isabel Mellon for critical evaluation of the manuscript. This work was supported by grants IRG-163H from the American Cancer Society, 4755 from the Council for Tobacco Research Inc. and CA72856 from the National Cancer Institute to G.-M.L. S.M. was supported in part by an NIEHS Training Grant (ES07266) and H.W. was supported in part by a Showa University School of Medicine Fellowship.
PY - 1998/3/1
Y1 - 1998/3/1
N2 - 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.
AB - 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.
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U2 - 10.1093/nar/26.5.1173
DO - 10.1093/nar/26.5.1173
M3 - Article
C2 - 9469823
AN - SCOPUS:0032029995
SN - 0305-1048
VL - 26
SP - 1173
EP - 1178
JO - Nucleic acids research
JF - Nucleic acids research
IS - 5
ER -