A DNA damage response screen identifies RHINO, a 9-1-1 and TopBP1 interacting protein required for ATR signaling.

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.
Mesh Terms:
Ataxia Telangiectasia Mutated Proteins, Carrier Proteins, Cell Cycle, Cell Cycle Proteins, Cell Line, Tumor, Chemokines, DNA Damage, DNA Repair, DNA-Binding Proteins, Exonucleases, Humans, Multiprotein Complexes, Nuclear Proteins, Protein-Serine-Threonine Kinases, Signal Transduction
Science
Date: Jun. 10, 2011
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