Science · 2007 · 536 citations · 16 references
Life SciencesCancer BiologyMolecular BiologyCell SignalingDna RepairMolecular OncologyCancer Cell SignalingCell Cycle ControlCell Cycle SignalingDna Damage RecognitionDna Damage SignalingSignal Transduction In CancerBrca1 FunctionBreast Cancer Susceptibility Protein 1Dna Damage Checkpoint SignalingDna Damage Response FociDna Damage Response PathwaysDna Damage Response SignalingG2/m Checkpoint ControlUbiquitin-mediated Dna Damage Signaling
Mutations in the breast cancer susceptibility gene 1 (BRCA1) are associated with an increased risk of breast and ovarian cancers. BRCA1 participates in the cellular DNA damage response. We report the identification of receptor-associated protein 80 (RAP80) as a BRCA1-interacting protein in humans. RAP80 contains a tandem ubiquitin-interacting motif domain, which is required for its binding with ubiquitin in vitro and its damage-induced foci formation in vivo. Moreover, RAP80 specifically recruits BRCA1 to DNA damage sites and functions with BRCA1 in G2/M checkpoint control. Together, these results suggest the existence of a ubiquitination-dependent signaling pathway involved in the DNA damage response.
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