Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Ubiquitin-Binding Protein RAP80 Mediates BRCA1-Dependent DNA Damage Response
Hongtae Kim,1
Junjie Chen,1*
Xiaochun Yu2*
Abstract:
Mutations in the breast cancer susceptibility gene 1 (BRCA1)are associated with an increased risk of breast and ovariancancers. BRCA1 participates in the cellular DNA damage response.We report the identification of receptor-associated protein80 (RAP80) as a BRCA1-interacting protein in humans. RAP80 containsa tandem ubiquitin-interacting motif domain, which is requiredfor its binding with ubiquitin in vitro and its damage-inducedfoci formation in vivo. Moreover, RAP80 specifically recruitsBRCA1 to DNA damage sites and functions with BRCA1 in G2/M checkpointcontrol. Together, these results suggest the existence of aubiquitination-dependent signaling pathway involved in the DNAdamage response.
1 Department of Therapeutic Radiology, Yale University School of Medicine, Post Office Box 208040, New Haven, CT 06520, USA. 2 Division of Molecular Medicine and Genetics, Department of Internal Medicine, University of Michigan Medical School, 109 Zina Pitcher Place, 1520 Biomedical Science Research Building, Ann Arbor, MI 48109, USA.
* To whom correspondence should be addressed. E-mail: Junjie.chen{at}yale.edu (J.C.); xiayu{at}med.umich.edu (X.Y.)
The editors suggest the following Related Resources on Science sites:
In Science Magazine
PERSPECTIVES
John H. J. Petrini (25 May 2007) Science316 (5828), 1138.
[DOI: 10.1126/science.1143700] |Summary »|Full Text »|PDF »
RESEARCH ARTICLES
Shuhei Matsuoka, Bryan A. Ballif, Agata Smogorzewska, E. Robert McDonald, III, Kristen E. Hurov, Ji Luo, Corey E. Bakalarski, Zhenming Zhao, Nicole Solimini, Yaniv Lerenthal, Yosef Shiloh, Steven P. Gygi, and Stephen J. Elledge (25 May 2007) Science316 (5828), 1160.
[DOI: 10.1126/science.1140321] |Abstract »|Full Text »|PDF »|Supporting Online Material »
In Science Signaling
EDITORS' CHOICE
L. Bryan Ray (29 May 2007) Sci. STKE2007 (388), tw189.
[DOI: 10.1126/stke.3882007tw189] |Abstract »
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
The ubiquitin landscape at DNA double-strand breaks.
MEPE/OF45 protects cells from DNA damage induced killing via stabilizing CHK1.
S. Liu, H. Wang, X. Wang, L. Lu, N. Gao, P. S. N. Rowe, B. Hu, and Y. Wang (2009)
Nucleic Acids Res.
|Abstract »|Full Text »|PDF »
Nucleotide excision repair-induced H2A ubiquitination is dependent on MDC1 and RNF8 and reveals a universal DNA damage response.
J. A. Marteijn, S. Bekker-Jensen, N. Mailand, H. Lans, P. Schwertman, A. M. Gourdin, N. P. Dantuma, J. Lukas, and W. Vermeulen (2009)
J. Cell Biol.
186, 835-847
|Abstract »|Full Text »|PDF »
A Regulatory Loop Composed of RAP80-HDM2-p53 Provides RAP80-enhanced p53 Degradation by HDM2 in Response to DNA Damage.
J. Yan, D. Menendez, X.-P. Yang, M. A. Resnick, and A. M. Jetten (2009)
J. Biol. Chem.
284, 19280-19289
|Abstract »|Full Text »|PDF »
PALB2 is an integral component of the BRCA complex required for homologous recombination repair.
MERIT40 controls BRCA1-Rap80 complex integrity and recruitment to DNA double-strand breaks.
G. Shao, J. Patterson-Fortin, T. E. Messick, D. Feng, N. Shanbhag, Y. Wang, and R. A. Greenberg (2009)
Genes & Dev.
23, 740-754
|Abstract »|Full Text »|PDF »
Accumulation of Pax2 Transactivation Domain Interaction Protein (PTIP) at Sites of DNA Breaks via RNF8-dependent Pathway Is Required for Cell Survival after DNA Damage.
Z. Gong, Y.-W. Cho, J.-E. Kim, K. Ge, and J. Chen (2009)
J. Biol. Chem.
284, 7284-7293
|Abstract »|Full Text »|PDF »
The Rap80-BRCC36 de-ubiquitinating enzyme complex antagonizes RNF8-Ubc13-dependent ubiquitination events at DNA double strand breaks.
G. Shao, D. R. Lilli, J. Patterson-Fortin, K. A. Coleman, D. E. Morrissey, and R. A. Greenberg (2009)
PNAS
106, 3166-3171
|Abstract »|Full Text »|PDF »
An Oligomerized 53BP1 Tudor Domain Suffices for Recognition of DNA Double-Strand Breaks.
O. Zgheib, K. Pataky, J. Brugger, and T. D. Halazonetis (2009)
Mol. Cell. Biol.
29, 1050-1058
|Abstract »|Full Text »|PDF »
Histone Ubiquitination Associates with BRCA1-Dependent DNA Damage Response.
J. Wu, M. S. Y. Huen, L.-Y. Lu, L. Ye, Y. Dou, M. Ljungman, J. Chen, and X. Yu (2009)
Mol. Cell. Biol.
29, 849-860
|Abstract »|Full Text »|PDF »
ATM Activation and Signaling under Hypoxic Conditions.
Z. Bencokova, M. R. Kaufmann, I. M. Pires, P. S. Lecane, A. J. Giaccia, and E. M. Hammond (2009)
Mol. Cell. Biol.
29, 526-537
|Abstract »|Full Text »|PDF »
Rapid Recruitment of BRCA1 to DNA Double-Strand Breaks Is Dependent on Its Association with Ku80.
L. Wei, L. Lan, Z. Hong, A. Yasui, C. Ishioka, and N. Chiba (2008)
Mol. Cell. Biol.
28, 7380-7393
|Abstract »|Full Text »|PDF »
Human Wrnip1 Is Localized in Replication Factories in a Ubiquitin-binding Zinc Finger-dependent Manner.
N. Crosetto, M. Bienko, R. G. Hibbert, T. Perica, C. Ambrogio, T. Kensche, K. Hofmann, T. K. Sixma, and I. Dikic (2008)
J. Biol. Chem.
283, 35173-35185
|Abstract »|Full Text »|PDF »
Distinct versus overlapping functions of MDC1 and 53BP1 in DNA damage response and tumorigenesis.
K. Minter-Dykhouse, I. Ward, M. S.Y. Huen, J. Chen, and Z. Lou (2008)
J. Cell Biol.
181, 727-735
|Abstract »|Full Text »|PDF »
Noncanonical E2 Variant-Independent Function of UBC13 in Promoting Checkpoint Protein Assembly.
M. S. Y. Huen, J. Huang, J. Yuan, M. Yamamoto, S. Akira, C. Ashley, W. Xiao, and J. Chen (2008)
Mol. Cell. Biol.
28, 6104-6112
|Abstract »|Full Text »|PDF »
RAP80 Responds to DNA Damage Induced by Both Ionizing Radiation and UV Irradiation and Is Phosphorylated at Ser205.
J. Yan, X.-P. Yang, Y.-S. Kim, and A. M. Jetten (2008)
Cancer Res.
68, 4269-4276
|Abstract »|Full Text »|PDF »
Ubc13/Rnf8 ubiquitin ligases control foci formation of the Rap80/Abraxas/Brca1/Brcc36 complex in response to DNA damage.
X. H. Yang and L. Zou (2007)
PNAS
104, 20645-20646
|Full Text »|PDF »
Orchestration of the DNA-Damage Response by the RNF8 Ubiquitin Ligase.
N. K. Kolas, J. R. Chapman, S. Nakada, J. Ylanko, R. Chahwan, F. D. Sweeney, S. Panier, M. Mendez, J. Wildenhain, T. M. Thomson, et al. (2007)
Science
318, 1637-1640
|Abstract »|Full Text »|PDF »
DNA Damage-Dependent Acetylation and Ubiquitination of H2AX Enhances Chromatin Dynamics.
T. Ikura, S. Tashiro, A. Kakino, H. Shima, N. Jacob, R. Amunugama, K. Yoder, S. Izumi, I. Kuraoka, K. Tanaka, et al. (2007)
Mol. Cell. Biol.
27, 7028-7040
|Abstract »|Full Text »|PDF »