PMID- 17438073
OWN - NLM
STAT- MEDLINE
DCOM- 20070522
LR  - 20181113
IS  - 0021-9525 (Print)
IS  - 1540-8140 (Electronic)
IS  - 0021-9525 (Linking)
VI  - 177
IP  - 2
DP  - 2007 Apr 23
TI  - Autophosphorylation of DNA-PKCS regulates its dynamics at DNA double-strand 
      breaks.
PG  - 219-29
AB  - The DNA-dependent protein kinase catalytic subunit (DNA-PK(CS)) plays an 
      important role during the repair of DNA double-strand breaks (DSBs). It is 
      recruited to DNA ends in the early stages of the nonhomologous end-joining (NHEJ) 
      process, which mediates DSB repair. To study DNA-PK(CS) recruitment in vivo, we 
      used a laser system to introduce DSBs in a specified region of the cell nucleus. 
      We show that DNA-PK(CS) accumulates at DSB sites in a Ku80-dependent manner, and 
      that neither the kinase activity nor the phosphorylation status of DNA-PK(CS) 
      influences its initial accumulation. However, impairment of both of these 
      functions results in deficient DSB repair and the maintained presence of 
      DNA-PK(CS) at unrepaired DSBs. The use of photobleaching techniques allowed us to 
      determine that the kinase activity and phosphorylation status of DNA-PK(CS) 
      influence the stability of its binding to DNA ends. We suggest a model in which 
      DNA-PK(CS) phosphorylation/autophosphorylation facilitates NHEJ by destabilizing 
      the interaction of DNA-PK(CS) with the DNA ends.
FAU - Uematsu, Naoya
AU  - Uematsu N
AD  - Department of Radiation Oncology, University of Texas Southwestern Medical 
      Center, Dallas, TX 75390, USA.
FAU - Weterings, Eric
AU  - Weterings E
FAU - Yano, Ken-ichi
AU  - Yano K
FAU - Morotomi-Yano, Keiko
AU  - Morotomi-Yano K
FAU - Jakob, Burkhard
AU  - Jakob B
FAU - Taucher-Scholz, Gisela
AU  - Taucher-Scholz G
FAU - Mari, Pierre-Olivier
AU  - Mari PO
FAU - van Gent, Dik C
AU  - van Gent DC
FAU - Chen, Benjamin P C
AU  - Chen BP
FAU - Chen, David J
AU  - Chen DJ
LA  - eng
GR  - P01 CA092584/CA/NCI NIH HHS/United States
GR  - R37 CA050519/CA/NCI NIH HHS/United States
GR  - 5-R37-CA050519-16/CA/NCI NIH HHS/United States
GR  - P01-CA92584/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20070416
PL  - United States
TA  - J Cell Biol
JT  - The Journal of cell biology
JID - 0375356
RN  - 0 (Antigens, Nuclear)
RN  - 0 (DNA-Binding Proteins)
RN  - 9007-49-2 (DNA)
RN  - EC 2.7.11.1 (DNA-Activated Protein Kinase)
RN  - EC 3.6.4.12 (Xrcc6 protein, human)
RN  - EC 4.2.99.- (Ku Autoantigen)
SB  - IM
MH  - Animals
MH  - Antigens, Nuclear/metabolism
MH  - CHO Cells
MH  - *Catalytic Domain
MH  - Cricetinae
MH  - Cricetulus
MH  - DNA/metabolism
MH  - *DNA Breaks, Double-Stranded
MH  - *DNA Repair
MH  - DNA-Activated Protein Kinase/chemistry/*metabolism
MH  - DNA-Binding Proteins/metabolism
MH  - Humans
MH  - Ku Autoantigen
MH  - Lasers
MH  - Phosphorylation
MH  - Photobleaching
PMC - PMC2064131
EDAT- 2007/04/18 09:00
MHDA- 2007/05/23 09:00
PMCR- 2007/10/23
CRDT- 2007/04/18 09:00
PHST- 2007/04/18 09:00 [pubmed]
PHST- 2007/05/23 09:00 [medline]
PHST- 2007/04/18 09:00 [entrez]
PHST- 2007/10/23 00:00 [pmc-release]
AID - jcb.200608077 [pii]
AID - 200608077 [pii]
AID - 10.1083/jcb.200608077 [doi]
PST - ppublish
SO  - J Cell Biol. 2007 Apr 23;177(2):219-29. doi: 10.1083/jcb.200608077. Epub 2007 Apr 
      16.