Stn1 supports Mec1 function in protecting stalled replication forks from degradation.
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-?C) exacerbates both phenotypes. Mechanistically, Stn1 opposes the resection activities of Mre11, Exo1, and Sgs1 by promoting Pol?-primase-dependent fill-in and by limiting their association with stalled replication forks, with the latter mechanism predominating in the suppression exerted by Stn1L60F. Thus, Stn1 works with the checkpoint to curb nuclease activity at sites of replication stress.
Mesh Terms:
Cell Cycle Proteins, Checkpoint Kinase 2, DNA Repair, DNA Replication, DNA, Single-Stranded, DNA-Binding Proteins, Endodeoxyribonucleases, Exodeoxyribonucleases, Humans, Intracellular Signaling Peptides and Proteins, Protein Serine-Threonine Kinases, RecQ Helicases, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins
Cell Cycle Proteins, Checkpoint Kinase 2, DNA Repair, DNA Replication, DNA, Single-Stranded, DNA-Binding Proteins, Endodeoxyribonucleases, Exodeoxyribonucleases, Humans, Intracellular Signaling Peptides and Proteins, Protein Serine-Threonine Kinases, RecQ Helicases, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins
PLoS Genet
Date: Oct. 01, 2025
PubMed ID: 41091836
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