Human DNA-(Cytosine-5) Methyltransferase-PCNA Complex as a Target for p21WAF1

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Science  26 Sep 1997:
Vol. 277, Issue 5334, pp. 1996-2000
DOI: 10.1126/science.277.5334.1996

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DNA–(cytosine-5) methyltransferase (MCMT) methylates newly replicated mammalian DNA, but the factors regulating this activity are unknown. Here, MCMT is shown to bind proliferating cell nuclear antigen (PCNA), an auxiliary factor for DNA replication and repair. Binding of PCNA requires amino acids 163 to 174 of MCMT, occurs in intact cells at foci of newly replicated DNA, and does not alter MCMT activity. A peptide derived from the cell cycle regulator p21WAF1 can disrupt the MCMT-PCNA interaction, which suggests that p21WAF1 may regulate methylation by blocking access of MCMT to PCNA. MCMT and p21WAF1 may be linked in a regulatory pathway, because the extents of their expression are inversely related in both SV40-transformed and nontransformed cells.

  • * Present address: Department of Genetics and Development, Columbia University, Hammer 1124, 701 West 168th Street, New York, NY 10032, USA.

  • To whom correspondence should be addressed. E-mail: mcblib{at}

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