Premature Cdk1/Cdc5/Mus81 pathway activation induces aberrant replication and deleterious crossover.

ABSTRACT: The error-free DNA damage tolerance (DDT) pathway is crucial for replication completion and genome integrity. Mechanistically, this process is driven by a switch of templates accompanied by sister chromatid junction (SCJ) formation. Here, we asked if DDT intermediate processing is temporarily regulated, and what impact such regulation may have on genome stability. We find that persistent DDT recombination intermediates are largely resolved before anaphase through a G2/M damage checkpoint-independent, but Cdk1/Cdc5-dependent pathway that proceeds via a previously described Mus81-Mms4-activating phosphorylation. The Sgs1-Top3- and Mus81-Mms4-dependent resolution pathways occupy different temporal windows in relation to replication, with the Mus81-Mms4 pathway being restricted to late G2/M. P

SUBMITTER: Szakal B 

PROVIDER: S-EPMC3630363 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature