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Science 26 September 1997:
Vol. 277. no. 5334, pp. 1996 - 2000
DOI: 10.1126/science.277.5334.1996
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Reports

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

Linda S.-H. Chuang, Hang-In Ian, Tong-Wey Koh, Huck-Hui Ng, Guoliang Xu, * Benjamin F. L. Li dagger

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.

L. S.-H. Chuang, H.-I. Ian, T.-W. Koh, H.-H. Ng, B. F. L. Li, Chemical Carcinogenesis Laboratory, Institute of Molecular and Cell Biology, National University of Singapore, Kent Ridge Crescent, Singapore 119260, Republic of Singapore.
G. Xu, Bioscience Centre, National University of Singapore, Kent Ridge Crescent, Singapore 119260, Republic of Singapore.
*   Present address: Department of Genetics and Development, Columbia University, Hammer 1124, 701 West 168th Street, New York, NY 10032, USA.

dagger    To whom correspondence should be addressed. E-mail: mcblib{at}leonis.nus.sg

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   Abstract »    Full Text »    PDF »
DNA Methyltransferase Deficiency Modifies Cancer Susceptibility in Mice Lacking DNA Mismatch Repair.
B. N. Trinh, T. I. Long, A. E. Nickel, D. Shibata, and P. W. Laird (2002)
Mol. Cell. Biol. 22, 2906-2917
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Methylation Matters: Modeling a Manageable Genome.
J. M. Ordway and T. Curran (2002)
Cell Growth Differ. 13, 149-162
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5' CpG island hypermethylation is associated with transcriptional silencing of the p21CIP1/WAF1/SDI1 gene and confers poor prognosis in acute lymphoblastic leukemia.
J. Roman-Gomez, J. A. Castillejo, A. Jimenez, M. G. Gonzalez, F. Moreno, M. d. C. Rodriguez, M. Barrios, J. Maldonado, and A. Torres (2002)
Blood 99, 2291-2296
   Abstract »    Full Text »    PDF »
Preferential Methylation of Unmethylated DNA by Mammalian de Novo DNA Methyltransferase Dnmt3a.
T. Yokochi and K. D. Robertson (2002)
J. Biol. Chem. 277, 11735-11745
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Functional Interaction of MutY Homolog with Proliferating Cell Nuclear Antigen in Fission Yeast, Schizosaccharomyces pombe.
D.-Y. Chang and A-L. Lu (2002)
J. Biol. Chem. 277, 11853-11858
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Cooperativity between DNA Methyltransferases in the Maintenance Methylation of Repetitive Elements.
G. Liang, M. F. Chan, Y. Tomigahara, Y. C. Tsai, F. A. Gonzales, E. Li, P. W. Laird, and P. A. Jones (2002)
Mol. Cell. Biol. 22, 480-491
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Lashings of DNA methylation, forkfuls of chromatin remodeling.
R. R. Meehan, S. Pennings, and I. Stancheva (2001)
Genes & Dev. 15, 3231-3236
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Reduced Rates of Gene Loss, Gene Silencing, and Gene Mutation in Dnmt1-Deficient Embryonic Stem Cells.
M. F. Chan, R. van Amerongen, T. Nijjar, E. Cuppen, P. A. Jones, and P. W. Laird (2001)
Mol. Cell. Biol. 21, 7587-7600
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Infection of Lymphoid Cells by Integration-Defective Human Immunodeficiency Virus Type 1 Increases De Novo Methylation.
J.-Y. Fang, J. A. Mikovits, R. Bagni, C. L. Petrow-Sadowski, and F. W. Ruscetti (2001)
J. Virol. 75, 9753-9761
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Synergistic Activation of Functional Estrogen Receptor (ER)-{alpha} by DNA Methyltransferase and Histone Deacetylase Inhibition in Human ER-{alpha}-negative Breast Cancer Cells.
X. Yang, D. L. Phillips, A. T. Ferguson, W. G. Nelson, J. G. Herman, and N. E. Davidson (2001)
Cancer Res. 61, 7025-7029
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Etoposide Induces the Dispersal of DNA Ligase I from Replication Factories.
A. Montecucco, R. Rossi, G. Ferrari, A. I. Scovassi, E. Prosperi, and G. Biamonti (2001)
Mol. Biol. Cell 12, 2109-2118
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Methylation matters.
J. F Costello and C. Plass (2001)
J. Med. Genet. 38, 285-303
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Reactivity of Anti-Proliferating Cell Nuclear Antigen (PCNA) Murine Monoclonal Antibodies and Human Autoantibodies to the PCNA Multiprotein Complexes Involved in Cell Proliferation.
Y. Takasaki, T. Kogure, K. Takeuchi, K. Kaneda, T. Yano, K. Hirokawa, S. Hirose, T. Shirai, and H. Hashimoto (2001)
J. Immunol. 166, 4780-4787
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hMSH3 and hMSH6 interact with PCNA and colocalize with it to replication foci.
H. E. Kleczkowska, G. Marra, T. Lettieri, and J. Jiricny (2001)
Genes & Dev. 15, 724-736
   Abstract »    Full Text »


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