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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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Mol. Cell. Biol. 22, 480-491
   Abstract »    Full Text »    PDF »
The spatio-temporal organization of DNA replication sites is identical in primary, immortalized and transformed mammalian cells.
D. S. Dimitrova and R. Berezney (2002)
J. Cell Sci. 115, 4037-4051
   Abstract »    Full Text »    PDF »
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
   Abstract »    Full Text »    PDF »
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
   Abstract »    Full Text »    PDF »
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
   Abstract »    Full Text »    PDF »
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
   Abstract »    Full Text »    PDF »
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
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Expression of DNA methyltransferases DNMT1, 3A, and 3B in normal hematopoiesis and in acute and chronic myelogenous leukemia.
S.-i. Mizuno, T. Chijiwa, T. Okamura, K. Akashi, Y. Fukumaki, Y. Niho, and H. Sasaki (2001)
Blood 97, 1172-1179
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Domain structure, localization, and function of DNA polymerase {eta}, defective in xeroderma pigmentosum variant cells.
P. Kannouche, B. C. Broughton, M. Volker, F. Hanaoka, L. H.F. Mullenders, and A. R. Lehmann (2001)
Genes & Dev. 15, 158-172
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Deoxyribonucleic Acid Hypomethylation of Male Germ Cells by Mitotic and Meiotic Exposure to 5-Azacytidine Is Associated with Altered Testicular Histology.
T. Doerksen, G. Benoit, and J. M. Trasler (2000)
Endocrinology 141, 3235-3244
   Abstract »    Full Text »    PDF »


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