ERK activity facilitates activation of the S-phase DNA damage checkpoint by modulating ATR function

Although Erk kinase has been recently reported to function in the DNA damage response, the mechanism governing this process is unknown. We report here that hydroxyurea (HU) activates Erk via MEK1, a process that is sensitized by a constitutively active MEK1 (MEK1Q56P) and attenuated by a dominant-negative MEK1 (MEK1K97M). While ectopic MEK1Q56P sensitized HU-induced S-phase arrest, inhibition of Erk activation via U0126, PD98059, and MEK1K97M …