Volume 17 Issue 2, February 2007: 100-116
ORIGINAL ARTICLES
Cell polarity protein Par3 complexes with DNA-PK via Ku70 and regulates DNA double-strand break repair
Longhou Fang1, 2, YiGuo Wang1, 2, Dan Du1, 2, Guang Yang1, 2, Tim Tak Kwok3, Siu Kai Kong3, Benjamin Chen4, David J Chen4, Zhengjun Chen1,5
1Key Laboratory of Proteomics and Laboratory of Molecular Cell Biology, 2SHARF Laboratory, Institute of Biochemistry and Cell
Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 3Graduate School of the Chinese Academy of
Sciences, Shanghai 200031, China; 4Department of Biochemistry, The Chinese University of Hong Kong, Hong Kong SAR, China;
5Division of Molecular Radiation Biology, Department of Radiation Oncology, University of Texas Southwestern Medical Center,
Dallas, Texas, USA
Correspondence: Zhengjun Chen(zjchen@sibs.ac.cn)
The partitioning-defective 3 (Par3), a key component in the conserved Par3/Par6/aPKC complex, plays fundamental
roles in cell polarity. Herein we report the identification of Ku70 and Ku80 as novel Par3-interacting proteins through
an
in vitro binding assay followed by liquid chromatography-tandem mass spectrometry. Ku70/Ku80 proteins are two
key regulatory subunits of the DNA-dependent protein kinase (DNA-PK), which plays an essential role in repairing
double-strand DNA breaks (DSBs). We determined that the nuclear association of Par3 with Ku70/Ku80 was enhanced
by γ-irradiation (IR), a potent DSB inducer. Furthermore, DNA-PKcs, the catalytic subunit of DNA-PK, interacted with
the Par3/Ku70/Ku80 complex in response to IR. Par3 over-expression or knockdown was capable of up- or downregulating
DNA-PK activity, respectively. Moreover, the Par3 knockdown cells were found to be defective in random plasmid
integration, defective in DSB repair following IR, and radiosensitive, phenotypes similar to that of Ku70 knockdown
cells. These findings identify Par3 as a novel component of the DNA-PK complex and implicate an unexpected link of
cell polarity to DSB repair.
Cell Research (2007) 17:100-116. doi: 10.1038/sj.cr.7310145; published online 6 February 2007
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