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Author  |
Zardo, G.; Reale, A.; Passananti, C.; Pradhan, S.; Buontempo, S.; De Matteis, G.; Adams, R.L.P.; Caiafa, P. |
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Title |
Inhibition of poly(ADP-ribosyl)ation induces DNA hypermethylation: a possible molecular mechanism |
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Journal Article |
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Year |
2002 |
Publication |
The FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology |
Abbreviated Journal |
Faseb J |
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Volume |
16 |
Issue |
10 |
Pages |
1319-1321 |
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Keywords |
Animals; Benzamides/pharmacology; Cell Line; CpG Islands; Cyclin-Dependent Kinase Inhibitor p21; Cyclins/genetics/metabolism; DNA/metabolism; DNA (Cytosine-5-)-Methyltransferase/genetics/metabolism; DNA Methylation; Enzyme Inhibitors/pharmacology; Mice; Models, Genetic; Poly(ADP-ribose) Polymerases/antagonists & inhibitors; Precipitin Tests; Proliferating Cell Nuclear Antigen/metabolism; Proto-Oncogene Proteins c-fos/biosynthesis/genetics; RNA, Messenger/biosynthesis; Up-Regulation |
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Abstract |
The pattern of DNA methylation established during embryonic development is necessary for the control of gene expression and is preserved during the replicative process. DNA regions of about 1-2 kb in size, termed CpG islands and located mostly in the promoter regions of housekeeping genes, are protected from methylation, despite being about 6-10 times richer in the dinucleotide CpG than the rest of DNA. Their unmethylated state guarantees the expression of the corresponding housekeeping genes. At present, the mechanism by which CpG islands remain protected from methylation is not clear. However, some results suggest that poly(ADP-ribosyl)ation, an enzymatic process that introduces a postsynthetic modification onto chromatin proteins, might be involved. Here we show in L929 mouse fibroblast cells that inhibition of poly(ADP-ribose) polymerase(s) at different cell-cycle phases increases the mRNA and protein levels of the major maintenance DNA methyltransferase (DNMT1) in G1/S border. Increase of DNMT1 results in a premature PCNA-DNMT1 complex formation, which facilitates robust maintenance, as well as de novo DNA methylation processes during the G1/S border, which leads to abnormal hypermethylation. |
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Address |
Department of Cellular Biotechnologies and Haematology, University of Rome La Sapienza, Rome, Italy |
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English |
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ISSN |
0892-6638 |
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Notes |
PMID:12154007 |
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Call Number |
pubs @ support @ |
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9842 |
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