Abstract
Nucleolytic processing by nucleases can be a relevant mechanism to allow repair/restart of stalled replication forks. However, nuclease action needs to be controlled to prevent overprocessing of damaged replication forks that can be detrimental to genome stability. The checkpoint protein Rad9/53BP1 is known to limit nucleolytic degradation (resection) of DNA double-strand breaks (DSBs) in both yeast and mammals. Here, we show that loss of the inhibition that Rad9 exerts on resection exacerbates the sensitivity to replication stress of Mec1/ATR-defective yeast cells by exposing stalled replication forks to Dna2-dependent degradation. This Rad9 protective function is independent of checkpoint activation and relies mainly on Rad9-Dpb11 interaction. We propose that Rad9/53BP1 supports cell viability by protecting stalled replication forks from extensive resection when the intra-S checkpoint is not fully functional.
Original language | English |
---|---|
Journal | EMBO Reports |
Volume | 19 |
Issue number | 2 |
Pages (from-to) | 351-367 |
Number of pages | 17 |
ISSN | 1469-221X |
DOIs | |
Publication status | Published - 2018 |
Externally published | Yes |
Bibliographical note
© 2018 The Authors.Keywords
- Cell Cycle Proteins/metabolism
- DNA Replication
- Intracellular Signaling Peptides and Proteins/deficiency
- Microbial Viability
- Protein-Serine-Threonine Kinases/deficiency
- Saccharomyces cerevisiae/genetics
- Saccharomyces cerevisiae Proteins/metabolism
- Stress, Physiological
- Tumor Suppressor p53-Binding Protein 1/metabolism