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.

Modulation of DNMT1 activity by ADP-ribose polymers / Reale, Anna; DE MATTEIS, Giovanna; Giada, Galleazzi; Zampieri, Michele; Caiafa, Paola. - In: ONCOGENE. - ISSN 0950-9232. - ELETTRONICO. - 24:1(2005), pp. 13-19. [10.1038/sj.onc.1208005]

Modulation of DNMT1 activity by ADP-ribose polymers

REALE, Anna;DE MATTEIS, Giovanna;ZAMPIERI, Michele;CAIAFA, Paola
2005

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.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11573/235268
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