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BRCA1 is required for common-fragile-site stability via its G2/M checkpoint function.

Publication ,  Journal Article
Arlt, MF; Xu, B; Durkin, SG; Casper, AM; Kastan, MB; Glover, TW
Published in: Mol Cell Biol
August 2004

Common fragile sites are loci that form chromosome gaps or breaks when DNA synthesis is partially inhibited. Fragile sites are prone to deletions, translocations, and other rearrangements that can cause the inactivation of associated tumor suppressor genes in cancer cells. It was previously shown that ATR is critical to fragile-site stability and that ATR-deficient cells have greatly elevated fragile-site expression (A. M. Casper, P. Nghiem, M. F. Arlt, and T. W. Glover, Cell 111:779-789, 2002). Here we demonstrate that mouse and human cells deficient for BRCA1, due to mutation or knockdown by RNA interference, also have elevated fragile-site expression. We further show that BRCA1 functions in the induction of the G(2)/M checkpoint after aphidicolin-induced replication stalling and that this checkpoint function is involved in fragile-site stability. These data indicate that BRCA1 is important in fragile-site stability and that fragile sites are recognized by the G(2)/M checkpoint pathway, in which BRCA1 plays a key role. Furthermore, they suggest that mutations in BRCA1 or interacting proteins could lead to rearrangements at fragile sites in cancer cells.

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Published In

Mol Cell Biol

DOI

ISSN

0270-7306

Publication Date

August 2004

Volume

24

Issue

15

Start / End Page

6701 / 6709

Location

United States

Related Subject Headings

  • Transfection
  • RNA Interference
  • Precipitin Tests
  • Neoplasms
  • Mutation
  • Mitosis
  • Microscopy, Fluorescence
  • Mice
  • Humans
  • Genes, BRCA1
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Arlt, M. F., Xu, B., Durkin, S. G., Casper, A. M., Kastan, M. B., & Glover, T. W. (2004). BRCA1 is required for common-fragile-site stability via its G2/M checkpoint function. Mol Cell Biol, 24(15), 6701–6709. https://doi.org/10.1128/MCB.24.15.6701-6709.2004
Arlt, Martin F., Bo Xu, Sandra G. Durkin, Anne M. Casper, Michael B. Kastan, and Thomas W. Glover. “BRCA1 is required for common-fragile-site stability via its G2/M checkpoint function.Mol Cell Biol 24, no. 15 (August 2004): 6701–9. https://doi.org/10.1128/MCB.24.15.6701-6709.2004.
Arlt MF, Xu B, Durkin SG, Casper AM, Kastan MB, Glover TW. BRCA1 is required for common-fragile-site stability via its G2/M checkpoint function. Mol Cell Biol. 2004 Aug;24(15):6701–9.
Arlt, Martin F., et al. “BRCA1 is required for common-fragile-site stability via its G2/M checkpoint function.Mol Cell Biol, vol. 24, no. 15, Aug. 2004, pp. 6701–09. Pubmed, doi:10.1128/MCB.24.15.6701-6709.2004.
Arlt MF, Xu B, Durkin SG, Casper AM, Kastan MB, Glover TW. BRCA1 is required for common-fragile-site stability via its G2/M checkpoint function. Mol Cell Biol. 2004 Aug;24(15):6701–6709.

Published In

Mol Cell Biol

DOI

ISSN

0270-7306

Publication Date

August 2004

Volume

24

Issue

15

Start / End Page

6701 / 6709

Location

United States

Related Subject Headings

  • Transfection
  • RNA Interference
  • Precipitin Tests
  • Neoplasms
  • Mutation
  • Mitosis
  • Microscopy, Fluorescence
  • Mice
  • Humans
  • Genes, BRCA1