| Autor: |
Johnson, Robert E., Kovvali, Gopala K., Guzder, Sami N., Amin, Neelam S., Holm, Connie, Habraken, Yvette, Sung, Patrick, Prakash, Louise, Prakash, Satya |
| Zdroj: |
Journal of Biological Chemistry; November 1996, Vol. 271 Issue: 45 p27987-27990, 4p |
| Abstrakt: |
DNA mismatch repair plays a key role in the maintenance of genetic fidelity. Mutations in the human mismatch repair genes hMSH2, hMLH1, hPMS1, and hPMS2are 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 POL30gene 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 PMS1suggest that the pol30-104mutation 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. |
| Databáze: |
Supplemental Index |
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