CANCER Risk Factors in Breast and Ovarian Cancer

Mutations in breast cancer gene 1 (BRCA1) are a major cause of familial breast cancer. The BRCA1 protein functions in cellular responses to DNA damage, but its precise molecular actions are not fully understood. Two different approaches now show that the C-terminal domain of BRCA1 (BRCT), which is also found in other proteins that function in control of DNA damage, specifically binds to target sequences when serine or threonine residues in the target domain are phosphorylated. Yu et al. (see the Perspective by Caldecott) demonstrate the phosphorylation-dependent interaction of BRCA1 with BRCA1-associated C-terminal helicase and show that this interaction is required for a proper cellular response to DNA damage. Manke et al. used a proteomic strategy to identify BRCT domains in a screen for modules that would bind sequences preferentially phosphorylated by the phosphoinositide-like kinases ATM and ATR, which are activated in response to DNA damage.

X. Yu, C. C. S. Chini, M. He, G. Mer, J. Chen, The BRCT domain is a phospho-protein binding domain. Science 302, 639-642 (2003). [Abstract] [Full Text]

K. W. Caldecott, The BRCT domain: Signaling with friends? Science 302, 579-580 (2003). [Abstract] [Full Text]

I. A. Manke, D. M. Lowery, A. Nguyen, M. B. Yaffe, BRCT repeats as phosphopeptide-binding modules involved in protein targeting. Science 302, 636-639 (2003). [Abstract] [Full Text]

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In Science Signaling

EDITORS' CHOICE
Ubiquitin
Ubiquitination of Estrogen Receptor by BRCA1

John F. Foley (10 April 2007)
Sci. STKE 2007 (381), tw125. [DOI: 10.1126/stke.3812007tw125]
 |  Abstract »

In Science Magazine

PERSPECTIVES
CELL SIGNALING:
The BRCT Domain: Signaling with Friends?

Keith W. Caldecott (24 October 2003)
Science 302 (5645), 579. [DOI: 10.1126/science.1091463]
 |  Summary »  |  Full Text »  |  PDF »

REPORTS
BRCT Repeats As Phosphopeptide-Binding Modules Involved in Protein Targeting

Isaac A. Manke, Drew M. Lowery, Anhco Nguyen, and Michael B. Yaffe (24 October 2003)
Science 302 (5645), 636. [DOI: 10.1126/science.1088877]
 |  Abstract »  |  Full Text »  |  PDF »  |  Supporting Online Material »

REPORTS
The BRCT Domain Is a Phospho-Protein Binding Domain

Xiaochun Yu, Claudia Christiano Silva Chini, Miao He, Georges Mer, and Junjie Chen (24 October 2003)
Science 302 (5645), 639. [DOI: 10.1126/science.1088753]
 |  Abstract »  |  Full Text »  |  PDF »  |  Supporting Online Material »