THE CONTRIBUTION OF THE CYCLIN DEPENDENT KINASE INHIBITOR P21 TO THE CHK1 KINASE MEDIATED REGULATION

MARTÍN HABIF; JULIANA SPERONI; SABRINA F. MANSILLA; MARÍA BELÉN FEDERICO; MARÍA BELÉN VALLERGA; VANESA GOTTIFREDI

Buenos Aires, Argentina

Congreso; SAIB-49th Annual Meeting - Argentine Society for Biochemistry and Molecular Biology; 2013

SAIB - Argentine Society for Biochemistry and Molecular Biology

The cyclin dependent kinase (CDK) inhibitor p21 was recently characterized by our group as the first negative regulator of the DNA replication auxiliary process, translesion DNA synthesis (TLS). p21 inhibits the recruitment of TLS polymerases to UV damaged DNA and impairs replication fork progression, causing cell death and genomic instability. The degradation of p21 after UV irradiation is therefore critical to modulate the proper onset of TLS after UV irradiation. When searching for potential regulators of p21 degradation after UV irradiation I found that the depletion of the checkpoint effector kinase, Chk1, causes a substantial increase in the levels of p21. Given that Chk1 was suggested as a positive regulator of TLS, it is possible that Chk1 could control TLS, at least in part, though the negative modulation of p21 levels in cells. Experiments designed to analyze the potential link between TLS, Chk1 and p21 will be presented and discussed. Moreover, given the central role of Chk1 in the maintenance of genomic stability we will present evidence exploring the contribution of p21 to this important function of Chk1.