A novel kinase independent role of Chk1 in the replication of damaged DNA.

SPERONI J, MANSILLA S, FEDERICO MB, VALLERGA MB, HABIF M AND GOTTIFREDI V.

Conferencia; Gordon Research conference on DNA Damage; Mutation & Cancer.; 2012

Gordon Research Conferences

The Chk1 kinase is broadly known because of its function in the cellular response to the accumulation of damaged DNA. Since Chk1 activation requires its phosphorylation by ATR, it is expected that ATR or Chk1 downregulation should cause similar alterations in the signals triggered by DNA lesions. Intriguingly, we observed that Chk1 -but not ATR- promotes the progression of replication forks after UV irradiation. Strikingly, this novel role of Chk1 is independent of its kinase-domain and of its partnership with Claspin. Instead, we demonstrate that the ability of Chk1 to promote replication fork progression on damaged DNA templates relies on its recently identified PCNA-interacting motif, which is involved in its release from chromatin after DNA damage. Moreover, we observed that this motif of Chk1 also promotes the recruitment of the specialized DNA polymerase ?Ø (pol ?Ø?w into replication-associated foci. Since pol ?Ø is critical to allow DNA synthesis through UV-induced lesions, these observations provide a potential mechanism to explain how Chk1 promotes fork progression on damaged DNA templates. Thus, our data reveal an unexpected, specific and kinase-independent function of Chk1 during replication of damaged DNA.