G. Liberi et al., Srs2 DNA helicase is involved in checkpoint response and its regulation requires a functional Mec1-dependent pathway and Cdk1 activity, EMBO J, 19(18), 2000, pp. 5027-5038
In Saccharomyces cerevisiae the rate of DNA replication is slowed down in r
esponse to DNA damage as a result of checkpoint activation, which is mediat
ed by the Mec1 and Rad53 protein kinases, We found that the Srs2 DNA helica
se, which is involved in DNA repair and recombination, is phosphorylated in
response to intra-S DNA damage in a checkpoint-dependent manner. DNA damag
e-induced Srs2 phosphorylation also requires the activity of the cyclin-dep
endent kinase Cdk1, suggesting that the checkpoint pathway might modulate C
dk1 activity in response to DNA damage. Moreover, srs2 mutants fail to acti
vate Rad53 properly and to slow down DNA replication in response to intra-S
DNA damage. The residual Rad53 activity observed in srs2 cells depends upo
n the checkpoint proteins Rad17 and Rad24. Moreover, DNA damage-induced let
hality in rad17 mutants depends partially upon Srs2, suggesting that a func
tional Srs2 helicase causes accumulation of lethal events in a checkpoint-d
efective context. Altogether, our data implicate Srs2 in the Mec1 and Rad53
pathway and connect the checkpoint response to DNA repair and recombinatio
n.