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Rapid recruitment of BRCA1 to DNA double-strand breaks is dependent on its association with Ku80.

Publication ,  Journal Article
Wei, L; Lan, L; Hong, Z; Yasui, A; Ishioka, C; Chiba, N
Published in: Mol Cell Biol
December 2008

BRCA1 is the first susceptibility gene to be linked to breast and ovarian cancers. Although mounting evidence has indicated that BRCA1 participates in DNA double-strand break (DSB) repair pathways, its precise mechanism is still unclear. Here, we analyzed the in situ response of BRCA1 at DSBs produced by laser microirradiation. The amino (N)- and carboxyl (C)-terminal fragments of BRCA1 accumulated independently at DSBs with distinct kinetics. The N-terminal BRCA1 fragment accumulated immediately after laser irradiation at DSBs and dissociated rapidly. In contrast, the C-terminal fragment of BRCA1 accumulated more slowly at DSBs but remained at the sites. Interestingly, rapid accumulation of the BRCA1 N terminus, but not the C terminus, at DSBs depended on Ku80, which functions in the nonhomologous end-joining (NHEJ) pathway, independently of BARD1, which binds to the N terminus of BRCA1. Two small regions in the N terminus of BRCA1 independently accumulated at DSBs and interacted with Ku80. Missense mutations found within the N terminus of BRCA1 in cancers significantly changed the kinetics of its accumulation at DSBs. A P142H mutant failed to associate with Ku80 and restore resistance to irradiation in BRCA1-deficient cells. These might provide a molecular basis of the involvement of BRCA1 in the NHEJ pathway of the DSB repair process.

Duke Scholars

Published In

Mol Cell Biol

DOI

EISSN

1098-5549

Publication Date

December 2008

Volume

28

Issue

24

Start / End Page

7380 / 7393

Location

United States

Related Subject Headings

  • Ubiquitin-Protein Ligases
  • Tumor Suppressor Proteins
  • Recombinant Fusion Proteins
  • Peptide Fragments
  • Mutation, Missense
  • Lasers
  • Ku Autoantigen
  • Humans
  • Histones
  • Female
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Wei, L., Lan, L., Hong, Z., Yasui, A., Ishioka, C., & Chiba, N. (2008). Rapid recruitment of BRCA1 to DNA double-strand breaks is dependent on its association with Ku80. Mol Cell Biol, 28(24), 7380–7393. https://doi.org/10.1128/MCB.01075-08
Wei, Leizhen, Li Lan, Zehui Hong, Akira Yasui, Chikashi Ishioka, and Natsuko Chiba. “Rapid recruitment of BRCA1 to DNA double-strand breaks is dependent on its association with Ku80.Mol Cell Biol 28, no. 24 (December 2008): 7380–93. https://doi.org/10.1128/MCB.01075-08.
Wei L, Lan L, Hong Z, Yasui A, Ishioka C, Chiba N. Rapid recruitment of BRCA1 to DNA double-strand breaks is dependent on its association with Ku80. Mol Cell Biol. 2008 Dec;28(24):7380–93.
Wei, Leizhen, et al. “Rapid recruitment of BRCA1 to DNA double-strand breaks is dependent on its association with Ku80.Mol Cell Biol, vol. 28, no. 24, Dec. 2008, pp. 7380–93. Pubmed, doi:10.1128/MCB.01075-08.
Wei L, Lan L, Hong Z, Yasui A, Ishioka C, Chiba N. Rapid recruitment of BRCA1 to DNA double-strand breaks is dependent on its association with Ku80. Mol Cell Biol. 2008 Dec;28(24):7380–7393.

Published In

Mol Cell Biol

DOI

EISSN

1098-5549

Publication Date

December 2008

Volume

28

Issue

24

Start / End Page

7380 / 7393

Location

United States

Related Subject Headings

  • Ubiquitin-Protein Ligases
  • Tumor Suppressor Proteins
  • Recombinant Fusion Proteins
  • Peptide Fragments
  • Mutation, Missense
  • Lasers
  • Ku Autoantigen
  • Humans
  • Histones
  • Female