Ubiquitin-binding protein RAP80 mediates BRCA1-dependent DNA damage response.
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.
Kim
Hongtae
H
Department of Therapeutic Radiology, Yale University School of Medicine, Post Office Box 208040, New Haven, CT 06520, USA.
Chen
Junjie
J
Yu
Xiaochun
X
D000595:Amino Acid Sequence; D019313:BRCA1 Protein / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D004247:DNA / Q000378:metabolism* / Q000528:radiation effects; D004249:DNA Damage; D004260:DNA Repair / Q000502:physiology*; D004268:DNA-Binding Proteins; D006367:HeLa Cells; D056488:Histone Chaperones; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D034741:RNA, Small Interfering; D011839:Radiation, Ionizing; D025801:Ubiquitin / Q000378:metabolism*
D019313:BRCA1 Protein; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D056488:Histone Chaperones; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; C466234:UIMC1 protein, human; D025801:Ubiquitin; D004247:DNA