Persistently bound Ku at DNA ends attenuates DNA end resection and homologous recombination

Zhengping Shao, Anthony J. Davis, Kazi R. Fattah, Sairei So, Jingxin Sun, Kyung Jong Lee, Lynn Harrison, Jun Yang, David J. Chen

Research output: Contribution to journalArticle

47 Scopus citations

Abstract

DNA double strand breaks (DSBs) are repaired by non-homologous end joining (NHEJ) or homologous recombination (HR). The DNA cell cycle stage and resection of the DSB ends are two key mechanisms which are believed to push DSB repair to the HR pathway. Here, we show that the NHEJ factor Ku80 associates with DSBs in S phase, when HR is thought to be the preferred repair pathway, and its dynamics/kinetics at DSBs is similar to those observed for Ku80 in non-S phase in mammalian cells. A Ku homolog from Mycobacterium tuberculosis binds to and is retained at DSBs in S phase and was used as a tool to determine if blocking DNA ends affects end resection and HR in mammalian cells. A decrease in DNA end resection, as marked by IR-induced RPA, BrdU, and Rad51 focus formation, and HR are observed when Ku deficient rodent cells are complemented with Mt-Ku. Together, this data suggests that Ku70/80 binds to DSBs in all cell cycle stages and is likely actively displaced from DSB ends to free the DNA ends for DNA end resection and thus HR to occur.

Original languageEnglish (US)
Pages (from-to)310-316
Number of pages7
JournalDNA repair
Volume11
Issue number3
DOIs
StatePublished - Mar 1 2012

Keywords

  • DNA double-strand breaks
  • DNA end resection
  • Homologous recombination
  • Ku70/80
  • Non-homologous end-joining

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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