Stn1 supports Mec1 function in protecting stalled replication forks from degradation.

ABSTRACT: Replication stress threatens genome integrity by exposing replication forks to nucleolytic degradation. In both yeast and humans, the checkpoint kinases Mec1 and Rad53 limit deleterious single-stranded DNA (ssDNA), yet the protective mechanisms remain incompletely defined. Here, we identify a role for the CST subunit Stn1 in cooperating with Mec1 to restrain ssDNA formation under nucleotide depletion. A gain-of-function allele (stn1-L60F) suppresses the sensitivity to replication stress of Mec1-deficient cells and reduces ssDNA at stalled replication forks, whereas a loss-of-function truncation (stn1-ΔC) exacerbates both phenotypes. Mechanistically, Stn1 opposes the resection activities of Mre11, Exo1, and Sgs1 by promoting Polα-primase-dependent fill-in and by limiting their association w

SUBMITTER: Casari E 

PROVIDER: S-EPMC12548912 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature