TY - JOUR
T1 - Evidence for involvement of yeast proliferating cell nuclear antigen in DNA mismatch repair
AU - Johnson, Robert E.
AU - Kovvali, Gopala K.
AU - Guzder, Sami N.
AU - Amin, Neelam S.
AU - Holm, Connie
AU - Habraken, Yvette
AU - Sung, Patrick
AU - Prakash, Louise
AU - Prakash, Satya
PY - 1996
Y1 - 1996
N2 - DNA mismatch repair plays a key role in the maintenance of genetic fidelity. Mutations in the human mismatch repair genes hMSH2, hMLH1, hPMS1, and hPMS2 are associated with hereditary nonpolyposis colorectal cancer. The proliferating cell nuclear antigen (PCNA) is essential for DNA replication, where it acts as a processivity factor. Here, we identify a point mutation, pol30-104, in the Saccharomyces cerevisiae POL30 gene encoding PCNA that increases the rate of instability of simple repetitive DNA sequences and raises the rate of spontaneous forward mutation. Epistasis analyses with mutations in mismatch repair genes MSH2, MLH1, and PMS1 suggest that the pol30-104 mutation impairs MSH2/MLH1/PMS1-dependent mismatch repair, consistent with the hypothesis that PCNA functions in mismatch repair. MSH2 functions in mismatch repair with either MSH3 or MSH6, and the MSH2-MSH3 and MSH2-MSH6 heterodimers have a role in the recognition of DNA mismatches. Consistent with the genetic data, we find specific interaction of PCNA with the MSH2-MSH3 heterodimer.
AB - DNA mismatch repair plays a key role in the maintenance of genetic fidelity. Mutations in the human mismatch repair genes hMSH2, hMLH1, hPMS1, and hPMS2 are associated with hereditary nonpolyposis colorectal cancer. The proliferating cell nuclear antigen (PCNA) is essential for DNA replication, where it acts as a processivity factor. Here, we identify a point mutation, pol30-104, in the Saccharomyces cerevisiae POL30 gene encoding PCNA that increases the rate of instability of simple repetitive DNA sequences and raises the rate of spontaneous forward mutation. Epistasis analyses with mutations in mismatch repair genes MSH2, MLH1, and PMS1 suggest that the pol30-104 mutation impairs MSH2/MLH1/PMS1-dependent mismatch repair, consistent with the hypothesis that PCNA functions in mismatch repair. MSH2 functions in mismatch repair with either MSH3 or MSH6, and the MSH2-MSH3 and MSH2-MSH6 heterodimers have a role in the recognition of DNA mismatches. Consistent with the genetic data, we find specific interaction of PCNA with the MSH2-MSH3 heterodimer.
UR - http://www.scopus.com/inward/record.url?scp=0029905194&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029905194&partnerID=8YFLogxK
U2 - 10.1074/jbc.271.45.27987
DO - 10.1074/jbc.271.45.27987
M3 - Article
C2 - 8910404
AN - SCOPUS:0029905194
SN - 0021-9258
VL - 271
SP - 27987
EP - 27990
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 45
ER -