Abstract
The carboxyl-terminal domain (BRCT) of the Breast Cancer Gene 1 (BRCA1) protein is an evolutionarily conserved module that exists in a large number of proteins from prokaryotes to eukaryotes. Although most BRCT domain-containing proteins participate in DNA-damage checkpoint or DNA-repair pathways, or both, the function of the BRCT domain is not fully understood. We show that the BRCA1 BRCT domain directly interacts with phosphorylated BRCA1-Associated Carboxyl-terminal Helicase (BACH1). This specific interaction between BRCA1 and phosphorylated BACH1 is cell cycle regulated and is required for DNA damage-induced checkpoint control during the transition from G2 to M phase of the cell cycle. Further, we show that two other BRCT domains interact with their respective physiological partners in a phosphorylation-dependent manner. Thirteen additional BRCT domains also preferentially bind phospho-peptides rather than nonphosphorylated control peptides. These data imply that the BRCT domain is a phospho-protein binding domain involved in cell cycle control.
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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Amino Acid Motifs
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BRCA1 Protein / chemistry*
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BRCA1 Protein / metabolism*
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Carrier Proteins / chemistry
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Carrier Proteins / metabolism
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Cell Cycle
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Cell Cycle Proteins*
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Cell Line
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DNA Damage
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DNA Repair
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DNA-Binding Proteins*
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E2F Transcription Factors
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Fanconi Anemia Complementation Group Proteins
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G2 Phase
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Humans
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Mitosis
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Mutation
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Nuclear Proteins
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Peptide Library
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Phosphoprotein Phosphatases / chemistry
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Phosphoprotein Phosphatases / metabolism
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Phosphoproteins / chemistry
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Phosphoproteins / genetics
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Phosphoproteins / metabolism*
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Phosphorylation
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Phosphoserine / metabolism
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Protein Binding
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Protein Structure, Tertiary
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RNA Helicases / chemistry
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RNA Helicases / genetics
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RNA Helicases / metabolism*
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RNA Polymerase II / metabolism
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RNA, Small Interfering
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Recombinant Fusion Proteins / chemistry
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Recombinant Fusion Proteins / metabolism
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Transcription Factors / metabolism
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Transfection
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Tumor Cells, Cultured
Substances
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BRCA1 Protein
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Carrier Proteins
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Cell Cycle Proteins
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DNA-Binding Proteins
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E2F Transcription Factors
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Fanconi Anemia Complementation Group Proteins
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Nuclear Proteins
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Peptide Library
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Phosphoproteins
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RNA, Small Interfering
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Recombinant Fusion Proteins
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TOPBP1 protein, human
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Transcription Factors
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Phosphoserine
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RNA Polymerase II
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Phosphoprotein Phosphatases
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carboxy-terminal domain phosphatase
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BRIP1 protein, human
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RNA Helicases