PMID- 21954437
OWN - NLM
STAT- MEDLINE
DCOM- 20120314
LR  - 20211203
IS  - 1362-4962 (Electronic)
IS  - 0305-1048 (Print)
IS  - 0305-1048 (Linking)
VI  - 40
IP  - 2
DP  - 2012 Jan
TI  - A dual role of BRCA1 in two distinct homologous recombination mediated repair in 
      response to replication arrest.
PG  - 726-38
LID - 10.1093/nar/gkr748 [doi]
AB  - Homologous recombination (HR) is a major mechanism utilized to repair blockage of 
      DNA replication forks. Here, we report that a sister chromatid exchange (SCE) 
      generated by crossover-associated HR efficiently occurs in response to 
      replication fork stalling before any measurable DNA double-strand breaks (DSBs). 
      Interestingly, SCE produced by replication fork collapse following DNA DSBs 
      creation is specifically suppressed by ATR, a central regulator of the 
      replication checkpoint. BRCA1 depletion leads to decreased RPA2 phosphorylation 
      (RPA2-P) following replication fork stalling but has no obvious effect on RPA2-P 
      following replication fork collapse. Importantly, we found that BRCA1 promotes 
      RAD51 recruitment and SCE induced by replication fork stalling independent of 
      ATR. In contrast, BRCA1 depletion leads to a more profound defect in RAD51 
      recruitment and SCE induced by replication fork collapse when ATR is depleted. We 
      concluded that BRCA1 plays a dual role in two distinct HR-mediated repair upon 
      replication fork stalling and collapse. Our data established a molecular basis 
      for the observation that defective BRCA1 leads to a high sensitivity to agents 
      that cause replication blocks without being associated with DSBs, and also 
      implicate a novel mechanism by which loss of cell cycle checkpoints promotes 
      BRCA1-associated tumorigenesis via enhancing HR defect resulting from BRCA1 
      deficiency.
FAU - Feng, Zhihui
AU  - Feng Z
AD  - Department of Radiation Oncology, Washington University School of Medicine, 4511 
      Forest Park Boulevard, St. Louis, Missouri 63108, USA.
FAU - Zhang, Junran
AU  - Zhang J
LA  - eng
GR  - R01 CA154625/CA/NCI NIH HHS/United States
GR  - R01CA154625/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20110927
PL  - England
TA  - Nucleic Acids Res
JT  - Nucleic acids research
JID - 0411011
RN  - 0 (BRCA1 Protein)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (DNA, Single-Stranded)
RN  - 0 (Replication Protein A)
RN  - EC 2.7.11.1 (ATR protein, human)
RN  - EC 2.7.11.1 (Ataxia Telangiectasia Mutated Proteins)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.7.- (Rad51 Recombinase)
SB  - IM
MH  - Ataxia Telangiectasia Mutated Proteins
MH  - BRCA1 Protein/analysis/*physiology
MH  - Cell Cycle Proteins/antagonists & inhibitors/physiology
MH  - Cell Line
MH  - DNA Breaks, Double-Stranded
MH  - *DNA Repair
MH  - *DNA Replication
MH  - DNA, Single-Stranded/chemistry
MH  - Genomic Instability
MH  - *Homologous Recombination
MH  - Humans
MH  - Protein Serine-Threonine Kinases/antagonists & inhibitors/physiology
MH  - Rad51 Recombinase/analysis
MH  - Replication Protein A/metabolism
MH  - Sister Chromatid Exchange
PMC - PMC3258139
EDAT- 2011/09/29 06:00
MHDA- 2012/03/15 06:00
PMCR- 2011/09/27
CRDT- 2011/09/29 06:00
PHST- 2011/09/29 06:00 [entrez]
PHST- 2011/09/29 06:00 [pubmed]
PHST- 2012/03/15 06:00 [medline]
PHST- 2011/09/27 00:00 [pmc-release]
AID - gkr748 [pii]
AID - 10.1093/nar/gkr748 [doi]
PST - ppublish
SO  - Nucleic Acids Res. 2012 Jan;40(2):726-38. doi: 10.1093/nar/gkr748. Epub 2011 Sep 
      27.