Cell Signaling Technology

Product Pathways - DNA Damage

Phospho-BRCA1 (Ser1524) Antibody #9009

Applications Reactivity Sensitivity MW (kDa) Source
W H Endogenous 220 Rabbit

Applications Key:  W=Western Blotting
Reactivity Key:  H=Human
Species cross-reactivity is determined by Western blot.

Protocols

Specificity / Sensitivity

Phospho-BRCA1 (Ser1524) Antibody detects endogenous levels of BRCA1 only when phosphorylated at Ser1524.

Source / Purification

Polyclonal antibodies are produced by immunizing rabbits with a synthetic phospho-peptide (KLH-coupled) corresponding to residues surrounding Ser1524 of human BRCA1. Antibodies are purified by protein A and peptide affinity chromatography.

Western Blotting

Western Blotting

Western blot analysis of untreated and UV-treated (50 mJ/cm2,30 min) HeLa cells and HT-1376 cells, using Phospho-BRCA1 (Ser1524) Antibody (upper) and BRCA1 Antibody #9010 (lower).

Background

The breast cancer susceptibility proteins BRCA1 and BRCA2 are frequently mutated in cases of hereditary breast and ovarian cancers and have roles in multiple processes related to DNA damage, repair, cell cycle progression, transcription, ubiquitination and apoptosis (1-4). BRCA2 has been shown to be required for localization of Rad51 to sites of double stranded breaks (DSBs) in DNA, and cells lacking BRCA1 and BRCA2 cannot repair DSBs through the Rad51-dependent process of homologous recombination (HR) (5). Numerous DNA-damage induced phosphorylation sites on BRCA1 have been identified, including serines 988, 1189, 1387, 1423, 1457, 1524 and 1542, and kinases activated in a cell cycle-dependent manner, including Aurora A and CDK2, can also phosphorylate BRCA1 at Ser308 and Ser1497, respectively (6-10). Cell cycle-dependent phosphorylation of BRCA2 at Ser3291 by CDKs has been proposed as a mechanism to switch off HR as cells progress beyond S-phase by blocking the carboxy-terminal Rad51 binding site (11).

In Xenopus, in response to DNA damage, ATR-dependent and Claspin-mediated recruitment of BRCA1 leads to phosphorylation at Ser1524 (12).

  1. Rahman, N. and Stratton, M.R. (1998) Annu. Rev. Genet. 32, 95-121.
  2. Gayther, S. A. et al. (1999) Am. J. Hum. Genet. 65, 1021-1029.
  3. Kerr, P. and Ashworth, A. (2001) Curr. Biol. 11, R668-R676.
  4. Scully, R. and Livingston, D.M. (2000) Nature 408, 429-432.
  5. Tutt, A. and Ashworth, A. (2002) Trends Mol. Med. 8, 571-576.
  6. Okada, S. and Ouchi, T. (2003) J. Biol. Chem. 278, 2015-2020.
  7. Cortez, D. et al. (1999) Science 286, 1162-1166.
  8. Xu, B. et al. (2002) Cancer Res. 62, 4588-4591.
  9. Ouchi, M. et al. (2004) J. Biol. Chem. 279, 19643-19648.
  10. Ruffner, H. et al. (1999) Mol. Cell. Biol. 19, 4843-4854.
  11. Esashi, F. et al. (2005) Nature 434, 598-604.
  12. Lin, S. Y. et al. (2004) Proc. Natl. Acad. Sci. USA 101, 6484-6489.

Application References

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Companion Products

This product is for in vitro research use only and is not intended for use in humans or animals. This product is not intended for use as therapeutic or in diagnostic procedures.

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