title: Interaction of p21(CDKN1A) with PCNA regulates the histone acetyltransferase activity of p300 in nucleotide excision repair.
abstract: The cell-cycle inhibitor p21(CDKN1A) has been suggested to directly participate in DNA repair, thanks to the interaction with PCNA. Yet, its role has remained unclear. Among proteins interacting with both p21 and PCNA, the histone acetyltransferase (HAT) p300 has been shown to participate in DNA repair. Here we report evidence indicating that p21 protein localizes and interacts with both p300 and PCNA at UV-induced DNA damage sites. The interaction between p300 and PCNA is regulated in vivo by p21. Indeed, loss of p21, or its inability to bind PCNA, results in a prolonged binding to chromatin and an increased association of p300 with PCNA, in UV-irradiated cells. Concomitantly, HAT activity of p300 is reduced after DNA damage. In vitro experiments show that inhibition of p300 HAT activity induced by PCNA is relieved by p21, which disrupts the association between recombinant p300 and PCNA. These results indicate that p21 is required during DNA repair to regulate p300 HAT activity by disrupting its interaction with PCNA.
authors.affiliation: Dipartimento di Medicina Sperimentale, sez. Patologia Generale "C. Golgi", Università di Pavia, 27100 Pavia, Italy.
authors.forename: Ornella
authors.initials: O
authors.lastname: Cazzalini
authors.forename: Paola
authors.initials: P
authors.lastname: Perucca
authors.forename: Monica
authors.initials: M
authors.lastname: Savio
authors.forename: Daniela
authors.initials: D
authors.lastname: Necchi
authors.forename: Livia
authors.initials: L
authors.lastname: Bianchi
authors.forename: Lucia A
authors.initials: LA
authors.lastname: Stivala
authors.forename: Bernard
authors.initials: B
authors.lastname: Ducommun
authors.forename: A Ivana
authors.initials: AI
authors.lastname: Scovassi
authors.forename: Ennio
authors.initials: E
authors.lastname: Prosperi
mesh_terms: D002478:Cells, Cultured; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000032:analysis / Q000378:metabolism*; D004249:DNA Damage; D004260:DNA Repair; D006801:Humans; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism*; D050880:p300-CBP Transcription Factors / Q000032:analysis / Q000378:metabolism*; D000099224:p300-CBP-Associated Factor
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D018809:Proliferating Cell Nuclear Antigen; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor