PMID- 21969602
OWN - NLM
STAT- MEDLINE
DCOM- 20111230
LR  - 20211020
IS  - 1098-5549 (Electronic)
IS  - 0270-7306 (Print)
IS  - 0270-7306 (Linking)
VI  - 31
IP  - 23
DP  - 2011 Dec
TI  - The NF90/NF45 complex participates in DNA break repair via nonhomologous end 
      joining.
PG  - 4832-43
LID - 10.1128/MCB.05849-11 [doi]
AB  - Nuclear factor 90 (NF90), an RNA-binding protein implicated in the regulation of 
      gene expression, exists as a heterodimeric complex with NF45. We previously 
      reported that depletion of the NF90/NF45 complex results in a multinucleated 
      phenotype. Time-lapse microscopy revealed that binucleated cells arise by 
      incomplete abscission of progeny cells followed by fusion. Multinucleate cells 
      arose through aberrant division of binucleated cells and displayed abnormal 
      metaphase plates and anaphase chromatin bridges suggestive of DNA repair defects. 
      NF90 and NF45 are known to interact with the DNA-dependent protein kinase 
      (DNA-PK), which is involved in telomere maintenance and DNA repair by 
      nonhomologous end joining (NHEJ). We hypothesized that NF90 modulates the 
      activity of DNA-PK. In an in vitro NHEJ assay system, DNA end joining was reduced 
      by NF90/NF45 immunodepletion or by RNA digestion to an extent similar to that for 
      catalytic subunit DNA-PKcs immunodepletion. In vivo, NF90/NF45-depleted cells 
      displayed increased gamma-histone 2A.X foci, indicative of an accumulation of 
      double-strand DNA breaks (DSBs), and increased sensitivity to ionizing radiation 
      consistent with decreased DSB repair. Further, NF90/NF45 knockdown reduced 
      end-joining activity in vivo. These results identify the NF90/NF45 complex as a 
      regulator of DNA damage repair mediated by DNA-PK and suggest that structured RNA 
      may modulate this process.
FAU - Shamanna, Raghavendra A
AU  - Shamanna RA
AD  - Departments of Biochemistry and Molecular Biology, UMDNJ-New Jersey Medical 
      School, and Graduate School of Biomedical Sciences, UMDNJ, Newark, New Jersey 
      07101-1709, USA.
FAU - Hoque, Mainul
AU  - Hoque M
FAU - Lewis-Antes, Anita
AU  - Lewis-Antes A
FAU - Azzam, Edouard I
AU  - Azzam EI
FAU - Lagunoff, David
AU  - Lagunoff D
FAU - Pe'ery, Tsafi
AU  - Pe'ery T
FAU - Mathews, Michael B
AU  - Mathews MB
LA  - eng
GR  - R01 AI034552/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20111003
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (Antigens, Nuclear)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (ILF2 protein, human)
RN  - 0 (Multiprotein Complexes)
RN  - 0 (Nuclear Factor 45 Protein)
RN  - 0 (Nuclear Factor 90 Proteins)
RN  - 0 (Nuclear Proteins)
RN  - 9007-49-2 (DNA)
RN  - EC 2.7.11.1 (DNA-Activated Protein Kinase)
RN  - EC 2.7.11.1 (PRKDC protein, human)
RN  - EC 3.6.4.12 (Xrcc6 protein, human)
RN  - EC 4.2.99.- (Ku Autoantigen)
SB  - IM
MH  - Antigens, Nuclear/metabolism
MH  - Cell Fusion
MH  - Cell Nucleus/metabolism
MH  - DNA/metabolism/radiation effects
MH  - *DNA Breaks, Double-Stranded
MH  - *DNA End-Joining Repair
MH  - DNA-Activated Protein Kinase/metabolism
MH  - DNA-Binding Proteins/metabolism
MH  - Enzyme Assays
MH  - Gene Knockdown Techniques
MH  - HeLa Cells
MH  - Humans
MH  - Immunoprecipitation
MH  - Ku Autoantigen
MH  - Microscopy, Confocal
MH  - Microscopy, Fluorescence
MH  - Multiprotein Complexes/*metabolism
MH  - Nuclear Factor 45 Protein/genetics/*metabolism
MH  - Nuclear Factor 90 Proteins/genetics/*metabolism
MH  - Nuclear Proteins/metabolism
MH  - RNA Interference
MH  - Time-Lapse Imaging
PMC - PMC3232927
EDAT- 2011/10/05 06:00
MHDA- 2011/12/31 06:00
PMCR- 2012/06/01
CRDT- 2011/10/05 06:00
PHST- 2011/10/05 06:00 [entrez]
PHST- 2011/10/05 06:00 [pubmed]
PHST- 2011/12/31 06:00 [medline]
PHST- 2012/06/01 00:00 [pmc-release]
AID - MCB.05849-11 [pii]
AID - 5849-11 [pii]
AID - 10.1128/MCB.05849-11 [doi]
PST - ppublish
SO  - Mol Cell Biol. 2011 Dec;31(23):4832-43. doi: 10.1128/MCB.05849-11. Epub 2011 Oct 
      3.