The preference for error-free or error-prone postreplication repair is cell-cycle-dependent in Saccharomyces cerevisiae in response to low-dose methylmethanesulfonate.

Cells employ error-free or error-prone post-replication repair (PRR) processes to tolerate DNA damage. Here, we present a genome-wide screen for sensitivity to 0.001% methylmethanesulfonate (MMS). This relatively low dose is of particular interest because wild-type cells exhibit no discernible phenotypes in response to treatment, yet PRR mutants are unique among ...
repair mutants in their exquisite sensitivity to 0.001% MMS; thus, low-dose MMS treatment provides a distinctive opportunity to study post-replication repair processes. We show that upon exposure to low-dose MMS, a PRR-defective rad18Δ mutant stalls into a lengthy G2 arrest associated with the accumulation of ssDNA gaps. Consistent with previous results following UV-induced damage, reactivation of Rad18 even after a prolonged G2 arrest restores viability and genome integrity. We further show that PRR pathway preference in 0.001% MMS depends on timing and context; cells preferentially employ the error-free pathway in the S phase and do not require MEC1-dependent checkpoint activation for survival. However, when PRR is restricted to the G2 phase, cells utilize REV3-dependent translesion synthesis, which requires a MEC1-dependent delay and results in significant hypermutability.
Mol. Cell. Biol.
Date: Feb. 04, 2013
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