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.

Subscribe

Logo for

Science 332 (6035): 1313-1317

Copyright © 2011 by the American Association for the Advancement of Science

A DNA Damage Response Screen Identifies RHINO, a 9-1-1 and TopBP1 Interacting Protein Required for ATR Signaling

Cecilia Cotta-Ramusino,1,* E. Robert McDonald, III,1,*,{dagger} Kristen Hurov,1,{dagger} Mathew E. Sowa,2 J. Wade Harper,2 Stephen J. Elledge1,{ddagger}

Abstract: The DNA damage response (DDR) is brought about by a protein kinase cascade that orchestrates DNA repair through transcriptional and posttranslational mechanisms. Cell cycle arrest is a hallmark of the DDR. We screened for cells that lacked damage-induced cell cycle arrest and uncovered a critical role for Fanconi anemia and homologous recombination proteins in ATR (ataxia telangiectasia and Rad3-related) signaling. Three DDR candidates, the RNA processing protein INTS7, the circadian transcription factor CLOCK, and a previously uncharacterized protein RHINO, were recruited to sites of DNA damage. RHINO independently bound the Rad9-Rad1-Hus1 complex (9-1-1) and the ATR activator TopBP1. RHINO was recruited to sites of DNA damage by the 9-1-1 complex to promote Chk1 activation. We suggest that RHINO functions together with the 9-1-1 complex and TopBP1 to fully activate ATR.

1 Department of Genetics, Harvard University Medical School, Howard Hughes Medical Institute, Division of Genetics, Brigham and Women’s Hospital, Harvard University Medical School, Boston, MA 02115, USA.
2 Department of Pathology, Harvard University Medical School, Boston, MA 02115, USA.

* These authors contributed equally to this work.

{dagger} Present address: Novartis Institutes for Biomedical Research, 250 Massachusetts Avenue, Cambridge, MA 02139, USA.

{ddagger} To whom correspondence should be addressed. E-mail: selledge{at}genetics.med.harvard.edu


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
FANCJ Localization by Mismatch Repair Is Vital to Maintain Genomic Integrity after UV Irradiation.
S. Guillemette, A. Branagan, M. Peng, A. Dhruva, O. D. Scharer, and S. B. Cantor (2014)
Cancer Res. 74, 932-944
   Abstract »    Full Text »    PDF »
Phosphorylation of the Cryptochrome 1 C-terminal Tail Regulates Circadian Period Length.
P. Gao, S.-H. Yoo, K.-J. Lee, C. Rosensweig, J. S. Takahashi, B. P. Chen, and C. B. Green (2013)
J. Biol. Chem. 288, 35277-35286
   Abstract »    Full Text »    PDF »
A core hSSB1-INTS complex participates in the DNA damage response.
F. Zhang, T. Ma, and X. Yu (2013)
J. Cell Sci. 126, 4850-4855
   Abstract »    Full Text »    PDF »
DNA Damage Sensing by the ATM and ATR Kinases.
A. Marechal and L. Zou (2013)
Cold Spring Harb Perspect Biol 5, a012716
   Abstract »    Full Text »    PDF »
Global Impact of Salmonella Pathogenicity Island 2-secreted Effectors on the Host Phosphoproteome.
K. Imami, A. P. Bhavsar, H. Yu, N. F. Brown, L. D. Rogers, B. B. Finlay, and L. J. Foster (2013)
Mol. Cell. Proteomics 12, 1632-1643
   Abstract »    Full Text »    PDF »
Core circadian protein CLOCK is a positive regulator of NF-{kappa}B-mediated transcription.
M. L. Spengler, K. K. Kuropatwinski, M. Comas, A. V. Gasparian, N. Fedtsova, A. S. Gleiberman, I. I. Gitlin, N. M. Artemicheva, K. A. Deluca, A. V. Gudkov, et al. (2012)
PNAS 109, E2457-E2465
   Abstract »    Full Text »    PDF »
ATR maintains select progenitors during nervous system development.
Y. Lee, E. R. Shull, P.-O. Frappart, S. Katyal, V. Enriquez-Rios, J. Zhao, H. R. Russell, E. J. Brown, and P. J. McKinnon (2012)
EMBO J. 31, 1177-1189
   Abstract »    Full Text »    PDF »
Targeted Mutations in the ATR Pathway Define Agent-Specific Requirements for Cancer Cell Growth and Survival.
D. Wilsker, J. H. Chung, I. Pradilla, E. Petermann, T. Helleday, and F. Bunz (2012)
Mol. Cancer Ther. 11, 98-107
   Abstract »    Full Text »    PDF »
Wolf-Hirschhorn syndrome candidate 1 is involved in the cellular response to DNA damage.
I. Hajdu, A. Ciccia, S. M. Lewis, and S. J. Elledge (2011)
PNAS 108, 13130-13134
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882