title: Modulation of DNMT1 activity by ADP-ribose polymers.
abstract: We provided evidence that competitive inhibition of poly(ADP-ribose) polymerases in mammalian cells treated with 3-aminobenzamide causes DNA hypermethylation in the genome and anomalous hypermethylation of CpG islands. The molecular mechanism(s) connecting poly(ADP-ribosyl)ation with DNA methylation is still unknown. Here we show that DNMT1 is able to bind long and branched ADP-ribose polymers in a noncovalent way. Binding of poly ADP-ribose on DNMT1 inhibits DNA methyltransferase activity. Co-immunoprecipitation reactions indicate that PARP1 and DNMT1 are associated in vivo and that in this complex PARP1 is present in its ADP-ribosylated isoform. We suggest that this complex is catalytically inefficient in DNA methylation.
authors.affiliation: Department of Cellular Biotechnologies and Haematology, University of Rome 'La Sapienza', 00161 Rome, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Reale
authors.forename: Giovanna De
authors.initials: GD
authors.lastname: Matteis
authors.forename: Giada
authors.initials: G
authors.lastname: Galleazzi
authors.forename: Michele
authors.initials: M
authors.lastname: Zampieri
authors.forename: Paola
authors.initials: P
authors.lastname: Caiafa
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002467:Cell Nucleus / Q000201:enzymology / Q000235:genetics; D002499:Centrifugation, Density Gradient; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism*; D015254:DNA Modification Methylases / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism*; D011233:Precipitin Tests; D011485:Protein Binding
chemical_list: D011064:Poly Adenosine Diphosphate Ribose; D015254:DNA Modification Methylases; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human; C000619381:Dnmt1 protein, mouse