Abstract
The BRCA1 C-terminal (BRCT) domain has recently been implicated as a phospho-protein binding domain. We demonstrate here that a CTBP-interacting protein CtIP interacts with BRCA1 BRCT domains in a phosphorylation-dependent manner. The CtIP/BRCA1 complex only exists in G(2) phase and is required for DNA damage-induced Chk1 phosphorylation and the G(2)/M transition checkpoint. However, the CtIP/BRCA1 complex is not required for the damage-induced G(2) accumulation checkpoint, which is controlled by a separate BRCA1/BACH1 complex. Taken together, these data not only implicate CtIP as a critical player in cell cycle checkpoint control but also provide molecular mechanisms by which BRCA1 controls multiple cell cycle transitions after DNA damage.
Publication types
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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.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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BRCA1 Protein / chemistry*
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BRCA1 Protein / genetics
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BRCA1 Protein / metabolism*
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Cell Cycle*
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Cell Division
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Cell Line
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Checkpoint Kinase 1
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DNA Damage*
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Endodeoxyribonucleases
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Enzyme Activation
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G2 Phase
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Humans
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Multiprotein Complexes
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Mutagenesis, Site-Directed
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism*
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Phosphorylation
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Protein Binding
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Protein Kinases / metabolism
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Protein Structure, Tertiary
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RNA Interference
Substances
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BRCA1 Protein
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Carrier Proteins
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Multiprotein Complexes
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Nuclear Proteins
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Protein Kinases
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CHEK1 protein, human
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Checkpoint Kinase 1
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Endodeoxyribonucleases
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RBBP8 protein, human