title: A DNA damage response screen identifies RHINO, a 9-1-1 and TopBP1 interacting protein required for ATR signaling.
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.
authors.affiliation: Department of Genetics, Harvard University Medical School, Howard Hughes Medical Institute, Division of Genetics, Brigham and Women's Hospital, Boston, MA 02115, USA.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Cotta-Ramusino
authors.forename: E Robert
authors.initials: ER
authors.lastname: McDonald
authors.forename: Kristen
authors.initials: K
authors.lastname: Hurov
authors.forename: Mathew E
authors.initials: ME
authors.lastname: Sowa
authors.forename: J Wade
authors.initials: JW
authors.lastname: Harper
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Elledge
mesh_terms: D064007:Ataxia Telangiectasia Mutated Proteins; D002352:Carrier Proteins / Q000378:metabolism / Q000502:physiology*; D002453:Cell Cycle / Q000235:genetics; D018797:Cell Cycle Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D018925:Chemokines / Q000235:genetics / Q000502:physiology*; D019743:Chemokines, CXC; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000378:metabolism; D005092:Exonucleases / Q000378:metabolism; D006801:Humans; D046912:Multiprotein Complexes / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C508524:CXCL17 protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D018925:Chemokines; D019743:Chemokines, CXC; D004268:DNA-Binding Proteins; C549605:HUS1 protein, human; D046912:Multiprotein Complexes; D009687:Nuclear Proteins; C558820:RHNO1 protein, human; C110513:TOPBP1 protein, human; C069930:rad9 protein; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; D005092:Exonucleases; C113574:Rad1 protein, human