Ku stabilizes replication forks in the absence of Brc1.
DNA replication errors are a major source of genome instability in all organisms. In the fission yeast Schizosaccharomyces pombe, the DNA damage response protein Brc1 binds phospho-histone H2A (γH2A)-marked chromatin during S-phase, but how Brc1 protects genome integrity remains unclear. Here we report that the non-homologous end-joining (NHEJ) protein Ku ... becomes critical for survival of replication stress in brc1∆ cells. Ku's protective activity in brc1∆ cells does not involve its canonical NHEJ function or its roles in protecting telomeres or shielding DNA ends from Exo1 exonuclease. In brc1∆ pku80∆ cells, nuclear foci of Rad52 homologous recombination (HR) protein increase and Mus81-Eme1 Holliday junction resolvase becomes critical, indicating increased replication fork instability. Ku's localization at a ribosomal DNA replication fork barrier associated with frequent replisome-transcriptosome collisions increases in brc1∆ cells and increased collisions correlate with an enhanced requirement for Brc1. These data indicate that Ku stabilizes replication forks in the absence of Brc1.
Mesh Terms:
Antigens, Nuclear, DNA Damage, DNA End-Joining Repair, DNA Replication, DNA, Fungal, DNA-Binding Proteins, Genomic Instability, S Phase, Schizosaccharomyces, Schizosaccharomyces pombe Proteins
Antigens, Nuclear, DNA Damage, DNA End-Joining Repair, DNA Replication, DNA, Fungal, DNA-Binding Proteins, Genomic Instability, S Phase, Schizosaccharomyces, Schizosaccharomyces pombe Proteins
PLoS ONE
Date: May. 13, 2015
PubMed ID: 25965521
View in: Pubmed Google Scholar
Download Curated Data For This Publication
193147
Switch View:
- Interactions 11