Abstract
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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Amino Acid Sequence
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BRCA1 Protein / metabolism*
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Carrier Proteins / metabolism*
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Cell Cycle
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Cell Line, Tumor
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DNA / metabolism*
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DNA / radiation effects
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DNA Damage*
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DNA Repair / physiology*
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DNA-Binding Proteins
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HeLa Cells
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Histone Chaperones
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Humans
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Molecular Sequence Data
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Nuclear Proteins / metabolism*
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Protein Binding
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Protein Structure, Tertiary
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RNA, Small Interfering
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Radiation, Ionizing
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Ubiquitin / metabolism*
Substances
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BRCA1 Protein
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Carrier Proteins
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DNA-Binding Proteins
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Histone Chaperones
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Nuclear Proteins
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RNA, Small Interfering
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UIMC1 protein, human
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Ubiquitin
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DNA