Rad9/53BP1 protects stalled replication forks from degradation in Mec1/ATR-defective cells
Research output: Contribution to journal › Journal article › Research › peer-review
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.
|Number of pages
|Published - 2018
© 2018 The Authors.
- 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