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Rad9/53 BP 1 protects stalled replication forks from degradation in Mec1/ ATR ‐defective cells
Author(s) -
Villa Matteo,
Bonetti Diego,
Carraro Massimo,
Longhese Maria Pia
Publication year - 2018
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201744910
Subject(s) - microbiology and biotechnology , g2 m dna damage checkpoint , dna replication , biology , nuclease , homologous recombination , dna repair , dna , cell cycle checkpoint , genetics , cell cycle , cell
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 Rad9/53 BP 1 is known to limit nucleolytic degradation (resection) of DNA double‐strand breaks ( DSB s) 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 Rad9/53 BP 1 supports cell viability by protecting stalled replication forks from extensive resection when the intra‐S checkpoint is not fully functional.