Human DNA-(cytosine-5) methyltransferase-PCNA complex as a target for p21WAF1.
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 p21(WAF1) can disrupt the MCMT-PCNA interaction, 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 inversely related in both SV40-transformed and nontransformed cells.
Chuang
L S
LS
Chemical Carcinogenesis Laboratory, Institute of Molecular and Cell Biology, National University of Singapore, Kent Ridge Crescent, Singapore 119260, Republic of Singapore.
Ian
H I
HI
Koh
T W
TW
Ng
H H
HH
Xu
G
G
Li
B F
BF
D000595:Amino Acid Sequence; D002461:Cell Line, Transformed; D002467:Cell Nucleus / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000737:chemistry / Q000378:metabolism*; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism*; D004249:DNA Damage; D019175:DNA Methylation; D004260:DNA Repair; D004261:DNA Replication; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000494:pharmacology; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism / Q000494:pharmacology; D014407:Tumor Cells, Cultured
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D010455:Peptides; D018809:Proliferating Cell Nuclear Antigen; D011993:Recombinant Fusion Proteins; D004248:DNA (Cytosine-5-)-Methyltransferases