The contribution of the cyclin dependent kinase inhibitor p21 to the Chk1 kinase mediated regulation of genomic stability.

M HABIF, MB VALLERGA, S MANSILLA, MB FEDERICO, MA GONZÁLEZ BESTEIRO, A BERTOLIN, V GOTTIFREDI.

Buenos Aires

Conferencia; EMBO conference:Ubiquitin & ubiquitin-like proteins: At the crossroads from chromatin to protein.; 2014

EMBO Meetings

The CDK inhibitor p21 was recently characterized by our group as the first negative regulator for the recruitment of specialized DNA polymerases - effectors of the DNA replication auxiliary process translesion DNA synthesis- (TLS) - to UV damaged DNA, impairing replication fork progression and causing cell death and genomic instability. The degradation of p21 after UV irradiation is therefore critical to modulate this process. When searching for potential regulators of p21 stability, 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. Additionally, as specialized DNA polymerases are also involved in unperturbed DNA replication and in the maintenance of genomic stability under unstressed conditions, it is of significance to explore the contribution of this Chk1-p21 functional interaction in this cellular context. Experiments designed to analyze the potential link between 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.