CELL-CYCLE REGULATION OF THE HUMAN DNA MISMATCH REPAIR GENES HMSH2, HMLH1, AND HPMS2

Hereditary nonpolyposis colorectal cancer is a cancer susceptibility s yndrome that has been found to be caused by mutations in any of severa l genes involved in DNA mismatch repair, including hMSH2, hMLH1, or hP MS2, Recent reports have suggested that hMSH2 and hMLH1 have a role in the regulation of the cell cycle. To determine if these genes are cel l cycle regulated, we examined their mRNA and protein levels throughou t the cell cycle in IMR-90 normal human lung fibroblasts. We demonstra te that the levels of hMSH2 mRNA and protein do not change appreciably throughout the cell cycle, Although hMLH1 mRNA levels remained consta nt, there was a modest (approximately 50%) increase in its protein lev els during late G(1) and S phase, The levels of hPMS2 mRNA fluctuated (decreasing 50% in G(1) and increasing 50% in S phase), whereas hPMS2 protein levels increased 50% in late G(1) and S phase. Our data indica te that, at least in normal cells, the machinery responsible for the d etection and repair of mismatched DNA bases is present throughout the cell cycle.