Interaction of p21(CDKN1A) with PCNA regulates the histone acetyltransferase activity of p300 in nucleotide excision repair.
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.
Cazzalini
Ornella
O
Dipartimento di Medicina Sperimentale, sez. Patologia Generale "C. Golgi", Università di Pavia, 27100 Pavia, Italy.
Perucca
Paola
P
Savio
Monica
M
Necchi
Daniela
D
Bianchi
Livia
L
Stivala
Lucia A
LA
Ducommun
Bernard
B
Scovassi
A Ivana
AI
Prosperi
Ennio
E
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
D050759:Cyclin-Dependent Kinase Inhibitor p21; D018809:Proliferating Cell Nuclear Antigen; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor