P21Cip1/waf1 differentially regulates DNA replication and DNA repair-associated processes after UV

SORIA, G; SPERONI, J; PODHAJCER, O; PRIVES, C; GOTTIFREDI, V

JOURNAL OF CELL SCIENCE

Año: 2008

0021-9533

Although p21 up-regulation is required to block cell cycle progression after many types of genotoxic insults, UV irradiation triggers p21 proteolysis. The significance of the increased p21 turnover is unclear and might be associated to DNA repair. While the role of p21 in Nucleotide Excision Repair (NER) remains controversial, recent reports explore its effect on Translesion DNA Synthesis (TLS), a process that avoids replication blockage during S phase. Herein we analyze the effect of p21 on different PCNA-driven processes including DNA replication, NER and TLS. Whereas only the CDK binding domain of p21 is required for cell cycle arrest in unstressed cells; neither the CDK- nor the PCNA-binding domains of p21 are able to block early and late steps of NER. Intriguingly, through its PCNA binding domain, p21 inhibited the interaction of the TLS-polymerase, polη (pol eta) with PCNA and the assembly of polη foci after UV. Moreover, this obstruction correlates with accumulation of γH2AX and increased apoptosis. By showing that p21 is a negative regulator of PCNA/polη interaction our data unveil a link between efficient TLS and UV-induced degradation of p21.