PMID- 29253183
OWN - NLM
STAT- MEDLINE
DCOM- 20190722
LR  - 20190722
IS  - 1362-4962 (Electronic)
IS  - 0305-1048 (Print)
IS  - 0305-1048 (Linking)
VI  - 46
IP  - 2
DP  - 2018 Jan 25
TI  - Nuclear poly(A)-binding protein 1 is an ATM target and essential for DNA 
      double-strand break repair.
PG  - 730-747
LID - 10.1093/nar/gkx1240 [doi]
AB  - The DNA damage response (DDR) is an extensive signaling network that is robustly 
      mobilized by DNA double-strand breaks (DSBs). The primary transducer of the DSB 
      response is the protein kinase, ataxia-telangiectasia, mutated (ATM). Here, we 
      establish nuclear poly(A)-binding protein 1 (PABPN1) as a novel target of ATM and 
      a crucial player in the DSB response. PABPN1 usually functions in regulation of 
      RNA processing and stability. We establish that PABPN1 is recruited to the DDR as 
      a critical regulator of DSB repair. A portion of PABPN1 relocalizes to DSB sites 
      and is phosphorylated on Ser95 in an ATM-dependent manner. PABPN1 depletion 
      sensitizes cells to DSB-inducing agents and prolongs the DSB-induced G2/M 
      cell-cycle arrest, and DSB repair is hampered by PABPN1 depletion or elimination 
      of its phosphorylation site. PABPN1 is required for optimal DSB repair via both 
      nonhomologous end-joining (NHEJ) and homologous recombination repair (HRR), and 
      specifically is essential for efficient DNA-end resection, an initial, key step 
      in HRR. Using mass spectrometry analysis, we capture DNA damage-induced 
      interactions of phospho-PABPN1, including well-established DDR players as well as 
      other RNA metabolizing proteins. Our results uncover a novel ATM-dependent axis 
      in the rapidly growing interface between RNA metabolism and the DDR.
CI  - (c) The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic 
      Acids Research.
FAU - Gavish-Izakson, Michal
AU  - Gavish-Izakson M
AD  - Department of Human Molecular Genetics and Biochemistry, Sackler School of 
      Medicine, Tel Aviv University, Tel Aviv, Israel.
FAU - Velpula, Bhagya Bhavana
AU  - Velpula BB
AD  - Department of Human Molecular Genetics and Biochemistry, Sackler School of 
      Medicine, Tel Aviv University, Tel Aviv, Israel.
FAU - Elkon, Ran
AU  - Elkon R
AD  - Department of Human Molecular Genetics and Biochemistry, Sackler School of 
      Medicine, Tel Aviv University, Tel Aviv, Israel.
FAU - Prados-Carvajal, Rosario
AU  - Prados-Carvajal R
AD  - Centro Andaluz de Biologia Molecular y Medicina Regenerativa (CABIMER) and 
      Department of Genetics, University of Sevilla, Sevilla, Spain.
FAU - Barnabas, Georgina D
AU  - Barnabas GD
AD  - Department of Human Molecular Genetics and Biochemistry, Sackler School of 
      Medicine, Tel Aviv University, Tel Aviv, Israel.
FAU - Ugalde, Alejandro Pineiro
AU  - Ugalde AP
AD  - Division of Biological Stress Response, The Netherlands Cancer Institute, 
      Amsterdam, The Netherlands.
FAU - Agami, Reuven
AU  - Agami R
AD  - Division of Biological Stress Response, The Netherlands Cancer Institute, 
      Amsterdam, The Netherlands.
FAU - Geiger, Tamar
AU  - Geiger T
AD  - Department of Human Molecular Genetics and Biochemistry, Sackler School of 
      Medicine, Tel Aviv University, Tel Aviv, Israel.
FAU - Huertas, Pablo
AU  - Huertas P
AD  - Centro Andaluz de Biologia Molecular y Medicina Regenerativa (CABIMER) and 
      Department of Genetics, University of Sevilla, Sevilla, Spain.
FAU - Ziv, Yael
AU  - Ziv Y
AD  - Department of Human Molecular Genetics and Biochemistry, Sackler School of 
      Medicine, Tel Aviv University, Tel Aviv, Israel.
FAU - Shiloh, Yosef
AU  - Shiloh Y
AD  - Department of Human Molecular Genetics and Biochemistry, Sackler School of 
      Medicine, Tel Aviv University, Tel Aviv, Israel.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Nucleic Acids Res
JT  - Nucleic acids research
JID - 0411011
RN  - 0 (Nuclear Proteins)
RN  - 0 (PABPN1 protein, human)
RN  - 0 (Poly(A)-Binding Protein I)
RN  - 9007-49-2 (DNA)
RN  - EC 2.7.11.1 (Ataxia Telangiectasia Mutated Proteins)
SB  - IM
MH  - Ataxia Telangiectasia Mutated Proteins/genetics/*metabolism
MH  - Cell Line, Tumor
MH  - DNA/genetics/metabolism
MH  - *DNA Breaks, Double-Stranded
MH  - *DNA Repair
MH  - G2 Phase Cell Cycle Checkpoints/genetics
MH  - HeLa Cells
MH  - Humans
MH  - Nuclear Proteins/genetics/*metabolism
MH  - Phosphorylation
MH  - Poly(A)-Binding Protein I/genetics/*metabolism
MH  - Protein Binding
MH  - Protein Interaction Maps
MH  - RNA Interference
PMC - PMC5778506
EDAT- 2017/12/19 06:00
MHDA- 2019/07/23 06:00
PMCR- 2017/12/14
CRDT- 2017/12/19 06:00
PHST- 2017/01/12 00:00 [received]
PHST- 2017/12/04 00:00 [accepted]
PHST- 2017/12/19 06:00 [pubmed]
PHST- 2019/07/23 06:00 [medline]
PHST- 2017/12/19 06:00 [entrez]
PHST- 2017/12/14 00:00 [pmc-release]
AID - 4739366 [pii]
AID - gkx1240 [pii]
AID - 10.1093/nar/gkx1240 [doi]
PST - ppublish
SO  - Nucleic Acids Res. 2018 Jan 25;46(2):730-747. doi: 10.1093/nar/gkx1240.