UV-triggered p21 degradation facilitates damaged-DNA replication and preserves genomic stability

MANSILLA SF, SORIA G, VALLERGA MB, HABIF M, MARTINEZ LOPEZ W, PRIVES C AND GOTTIFREDI V

OXFORD UNIV PRESS

Lugar: Oxford; Año: 2013 vol. 41 p. 1 - 1

lthough many genotoxic treatments upregulate the cyclin kinase inhibitor p21, agents such as UV irradiation trigger p21 degradation. This suggests that p21 blocks a process relevant for the cellular response to UV. Here, we show that forced p21 stabilization after UV strongly impairs damaged-DNA replication, which is associated with permanent deficiencies in the recruitment of DNA polymerases from the Y family involved in translesion DNA synthesis), with the accumulation of DNA damage markers and increased genomic instability. Remarkably, such noxious effects disappear when disrupting the proliferating cell nuclear antigen (PCNA) interacting motif of stable p21, thus suggesting that the release of PCNA from p21 interaction is sufficient to allow the recruitment to PCNA of partners (such as Y polymerases) relevant for the UV response. Expression of degradable p21 only transiently delays early replication events and Y polymerase recruitment after UV irradiation. These temporary defects