INVESTIGADORES
PODHAJCER Osvaldo Luis
artículos
Título:
P21Cip1/Waf1 differentially regulates DNA replication and DNA-repair associated processes after UV
Autor/es:
SORIA G; SPERONI J; PODHAJCER OL; PRIVES C; GOTTIFREDI V
Revista:
JOURNAL OF CELL SCIENCE
Editorial:
COMPANY OF BIOLOGISTS LTD
Referencias:
Año: 2008 vol. 121 p. 3271 - 3282
ISSN:
0021-9533
Resumen:
Although p21 upregulation is required to block cell-cycle progression
following many types of genotoxic insult, UV irradiation triggers p21
proteolysis. The significance of the increased p21 turnover is unclear and might
be associated with DNA repair. While the role of p21 in nucleotide excision
repair (NER) remains controversial, recent reports have explored 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-binding nor the PCNA-binding domain of p21 is able to block early and late
steps of NER. Intriguingly, through its PCNA-binding domain, p21 inhibits the
interaction of the TLS polymerase, pol eta (pol eta), with PCNA and impairs the
assembly of pol eta foci after UV. Moreover, this obstruction correlates with
accumulation of phosphorylated H2AX and increased apoptosis. By showing that p21
is a negative regulator of PCNA-pol eta interaction, our data unveil a link
between efficient TLS and UV-induced degradation of p21.