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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

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