Rad9/53BP1 protects stalled replication forks from degradation in Mec1/ATR-defective cells
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Standard
Rad9/53BP1 protects stalled replication forks from degradation in Mec1/ATR-defective cells. / Villa, Matteo; Bonetti, Diego; Carraro, Massimo; Longhese, Maria Pia.
I: EMBO Reports, Bind 19, Nr. 2, 2018, s. 351-367.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Rad9/53BP1 protects stalled replication forks from degradation in Mec1/ATR-defective cells
AU - Villa, Matteo
AU - Bonetti, Diego
AU - Carraro, Massimo
AU - Longhese, Maria Pia
N1 - © 2018 The Authors.
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
KW - Cell Cycle Proteins/metabolism
KW - DNA Replication
KW - Intracellular Signaling Peptides and Proteins/deficiency
KW - Microbial Viability
KW - Protein-Serine-Threonine Kinases/deficiency
KW - Saccharomyces cerevisiae/genetics
KW - Saccharomyces cerevisiae Proteins/metabolism
KW - Stress, Physiological
KW - Tumor Suppressor p53-Binding Protein 1/metabolism
U2 - 10.15252/embr.201744910
DO - 10.15252/embr.201744910
M3 - Journal article
C2 - 29301856
VL - 19
SP - 351
EP - 367
JO - E M B O Reports
JF - E M B O Reports
SN - 1469-221X
IS - 2
ER -
ID: 241940552