Cell polarity protein Par3 complexes with DNA-PK via Ku70 and regulates DNA double-strand break repair

Longhou Fang, YiGuo Wang, Dan Du, Guang Yang, Tim Tak Kwok, Siu Kai Kong, Benjamin Chen, David J. Chen, Zhengjun Chen

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)100-116
Number of pages17
JournalCell Research
Volume17
Issue number2
DOIs
StatePublished - Feb 2007

Keywords

  • Cell polarity
  • DNA-PK
  • DSB repair
  • Ku70/Ku80 /Par3

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Cell polarity protein Par3 complexes with DNA-PK via Ku70 and regulates DNA double-strand break repair'. Together they form a unique fingerprint.

  • Cite this

    Fang, L., Wang, Y., Du, D., Yang, G., Tak Kwok, T., Kai Kong, S., Chen, B., Chen, D. J., & Chen, Z. (2007). Cell polarity protein Par3 complexes with DNA-PK via Ku70 and regulates DNA double-strand break repair. Cell Research, 17(2), 100-116. https://doi.org/10.1038/sj.cr.7310145