Abraxas and RAP80 Form a BRCA1 Protein Complex Required for the DNA Damage Response

作者: B. Wang , S. Matsuoka , B. A. Ballif , D. Zhang , A. Smogorzewska

DOI: 10.1126/SCIENCE.1139476

关键词:

摘要: The BRCT repeats of the breast and ovarian cancer predisposition protein BRCA1 are essential for tumor suppression. Phosphopeptide affinity proteomic analysis identified a protein, Abraxas, that directly binds through phospho-Ser-X-X-Phe motif. Abraxas to mutual exclusion BACH1 (BRCA1-associated C-terminal helicase) CtIP (CtBP-interacting protein), forming third type complex. recruits ubiquitin-interacting motif (UIM)–containing RAP80 BRCA1. Both were required DNA damage resistance, G2-M checkpoint control, repair. was optimal accumulation on damaged (foci) in response ionizing radiation, UIM domains alone capable foci formation. RAP80-Abraxas complex may help recruit sites part recognition ubiquitinated proteins.

参考文章(29)
Zhenkun Lou, Katherine Minter-Dykhouse, Sonia Franco, Monica Gostissa, Melissa A. Rivera, Arkady Celeste, John P. Manis, Jan van Deursen, André Nussenzweig, Tanya T. Paull, Frederick W. Alt, Junjie Chen, MDC1 Maintains Genomic Stability by Participating in the Amplification of ATM-Dependent DNA Damage Signals Molecular Cell. ,vol. 21, pp. 187- 200 ,(2006) , 10.1016/J.MOLCEL.2005.11.025
H. Ruffner, C. A. P. Joazeiro, D. Hemmati, T. Hunter, I. M. Verma, Cancer-predisposing mutations within the RING domain of BRCA1: Loss of ubiquitin protein ligase activity and protection from radiation hypersensitivity Proceedings of the National Academy of Sciences of the United States of America. ,vol. 98, pp. 5134- 5139 ,(2001) , 10.1073/PNAS.081068398
Leeju C Wu, Zhuo Wei Wang, Julia Tsou Tsan, Monique A Spillman, Anne Phung, Xie L Xu, Meng-Chun W Yang, Larn-Yuan Hwang, Anne M Bowcock, Richard Baer, None, Identification of a RING protein that can interact in vivo with the BRCA1 gene product. Nature Genetics. ,vol. 14, pp. 430- 440 ,(1996) , 10.1038/NG1296-430
X. Yu, The BRCT Domain Is a Phospho-Protein Binding Domain Science. ,vol. 302, pp. 639- 642 ,(2003) , 10.1126/SCIENCE.1088753
K. Nakanishi, Y.-G. Yang, A. J. Pierce, T. Taniguchi, M. Digweed, A. D. D'Andrea, Z.-Q. Wang, M. Jasin, Human Fanconi anemia monoubiquitination pathway promotes homologous DNA repair Proceedings of the National Academy of Sciences of the United States of America. ,vol. 102, pp. 1110- 1115 ,(2005) , 10.1073/PNAS.0407796102
Dorota Skowyra, Karen L Craig, Mike Tyers, Stephen J Elledge, J.Wade Harper, F-Box Proteins Are Receptors that Recruit Phosphorylated Substrates to the SCF Ubiquitin-Ligase Complex Cell. ,vol. 91, pp. 209- 219 ,(1997) , 10.1016/S0092-8674(00)80403-1
Xiaochun Yu, Shuang Fu, Maoyi Lai, Richard Baer, Junjie Chen, BRCA1 ubiquitinates its phosphorylation-dependent binding partner CtIP Genes & Development. ,vol. 20, pp. 1721- 1726 ,(2006) , 10.1101/GAD.1431006
R Baer, The BRCA1/BARD1 heterodimer, a tumor suppressor complex with ubiquitin E3 ligase activity. Current Opinion in Genetics & Development. ,vol. 12, pp. 86- 91 ,(2002) , 10.1016/S0959-437X(01)00269-6
David Cortez, Yi Wang, Jun Qin, Stephen J Elledge, Requirement of ATM-Dependent Phosphorylation of Brca1 in the DNA Damage Response to Double-Strand Breaks Science. ,vol. 286, pp. 1162- 1166 ,(1999) , 10.1126/SCIENCE.286.5442.1162