The checkpoint kinases Chk1 and Chk2 regulate the functional associations between hBRCA2 and Rad51 in response to DNA damage

E. M. Bahassi, J. L. Ovesen, A. L. Riesenberg, W. Z. Bernstein, Edward P Hasty, P. J. Stambrook

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

The cellular response to the introduction of double strand DNA breaks involves complexes of protein interactions that govern cell cycle checkpoint arrest and repair of the DNA lesions. The checkpoint kinases Chk1 and Chk2 phosphorylate the carboxy-terminal domain of hBRCA2, a protein involved in recombination-mediated DNA repair (HRR) and replication fork maintenance. Cells deficient in hBRCA2 are hypersensitive to DNA damaging agents. Phosphorylation of the residue in hBRCA2 targeted by the Chk1 and Chk2 kinases regulates its interaction with Rad51. Furthermore, the cell line lex1/lex2, which lacks the carboxy-terminal domain containing the phosphorylated residue, does not support localization of Rad51 to nuclear foci after exposure to UV or treatment with ionizing radiation (IR). The data show that either phosphorylation of Rad51 by Chk1 or phosphorylation of the carboxy-terminal domain of hBRCA2 by Chk1 or Chk2 plays a critical role in the binding of Rad51 to hBRCA2 and the subsequent recruitment of Rad51 to sites of DNA damage. While depletion of Chk1 from cells leads to loss of Rad51 localization to nuclear foci in response to replication arrest, cells lacking Chk2 also show a defect in Rad51 localization, but only in presence of double strand DNA breaks, indicating that each of these kinases may contribute somewhat differently to the formation of Rad51 nucleoprotein filaments depending on the type of DNA damage incurred by the cells.

Original languageEnglish (US)
Pages (from-to)3977-3985
Number of pages9
JournalOncogene
Volume27
Issue number28
DOIs
StatePublished - Jun 26 2008

Fingerprint

DNA Damage
Double-Stranded DNA Breaks
Phosphorylation
Cell Cycle Checkpoints
DNA Repair
Nucleoproteins
Ionizing Radiation
DNA Replication
Genetic Recombination
Proteins
Phosphotransferases
Maintenance
Cell Line
Checkpoint Kinase 1
DNA

Keywords

  • DNA damage
  • Homologous recombination
  • Phosphorylation
  • Rad51

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

The checkpoint kinases Chk1 and Chk2 regulate the functional associations between hBRCA2 and Rad51 in response to DNA damage. / Bahassi, E. M.; Ovesen, J. L.; Riesenberg, A. L.; Bernstein, W. Z.; Hasty, Edward P; Stambrook, P. J.

In: Oncogene, Vol. 27, No. 28, 26.06.2008, p. 3977-3985.

Research output: Contribution to journalArticle

Bahassi, E. M. ; Ovesen, J. L. ; Riesenberg, A. L. ; Bernstein, W. Z. ; Hasty, Edward P ; Stambrook, P. J. / The checkpoint kinases Chk1 and Chk2 regulate the functional associations between hBRCA2 and Rad51 in response to DNA damage. In: Oncogene. 2008 ; Vol. 27, No. 28. pp. 3977-3985.
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