HUMAN DNA (CYTOSINE-5) METHYLTRANSFERASE PCNA COMPLEX AS A TARGET FORP21(WAF1)

DNA-(cytosine-5) methyltransferase (MCMT) methylates newly replicated mammalian DNA, but the factors regulating this activity are unknown. H ere, MCMT is shown to bind proliferating cell nuclear antigen (PCNA), an auxiliary factor for DNA replication and repair. Binding of PCNA re quires amino acids 163 to 174 of MCMT, occurs in intact cells at fool of newly replicated DNA, and does not alter MCMT activity. A peptide d erived from the cell cycle regulator p21(WAF1) disrupt the MCMT-PCNA i nteraction, which suggests that p21(WAF1) may regulate methylation by blocking access of MCMT to PCNA, MCMT and p21(WAF1) may be linked in a regulatory pathway, because the extents of their expression are inver sely related in both SV40-transformed and nontransformed cells.