Structure and mechanism of BRCA1 BRCT domain recognition of phosphorylated BACH1 with implications for cancer

@article{Clapperton2004StructureAM,
  title={Structure and mechanism of BRCA1 BRCT domain recognition of phosphorylated BACH1 with implications for cancer},
  author={Julie A. Clapperton and Isaac A. Manke and Drew M. Lowery and Timmy Ho and Lesley F. Haire and Michael B. Yaffe and Stephen J. Smerdon},
  journal={Nature Structural \&Molecular Biology},
  year={2004},
  volume={11},
  pages={512-518}
}
Germline mutations in the BRCA1 tumor suppressor gene often result in a significant increase in susceptibility to breast and ovarian cancers. Although the molecular basis of their effects remains largely obscure, many mutations are known to target the highly conserved C-terminal BRCT repeats that function as a phosphoserine/phosphothreonine-binding module. We report the X-ray crystal structure at a resolution of 1.85 Å of the BRCA1 tandem BRCT domains in complex with a phosphorylated peptide… 
Insights into the Molecular Basis of Human Hereditary Breast Cancer from Studies of the BRCA1 BRCT Domain
  • J. Glover
  • Biology, Medicine
    Familial Cancer
  • 2005
TLDR
Structural and functional studies reveal that the N-terminal repeat is responsible for pSer binding while a groove at the interface of the two repeats recognizes the Phe, which indicates that missense variants identified in breast cancer screening programs often disrupt these interactions and these molecular defects may lead to an increased cancer risk.
Structural basis of phosphopeptide recognition by the BRCT domain of BRCA1
TLDR
Crystallographic and biochemical data suggest that the structural integrity of both binding sites is essential for peptide recognition, and the diminished peptide-binding capacity observed for cancer-associated BRCA1-BRCT variants may explain the enhanced cancer risks associated with these mutations.
Primary structure-based function characterization of BRCT domain replicates in BRCA1.
TLDR
This work has demonstrated p53-binding activity by an additional region, and confirmed previous results showing that two regions of BRCA1 protein bind p53 in vitro, and predicted five p 53-binding sites based on sequence analysis.
Impact of RING and BRCT Domain Mutations on BRCA1 Protein Stability, Localization and Recruitment to DNA Damage
TLDR
It is demonstrated that truncation of the BRCT domain greatly impairs the stability and nuclear localization of BRCA1 protein, and the data suggest that both the RING and BRCT domains are required for an early step in the function of BrcA1 during DNA repair: recruitment to the sites of DNA damage.
Structural basis of BACH1 phosphopeptide recognition by BRCA1 tandem BRCT domains.
TLDR
It is shown that a phenylalanine in the +3 position from the phosphoserine of BACH1 is bound to a conserved hydrophobic pocket formed between the two BRCT domains and that recognition of the phosphate group is mediated by lysine and serine side chains from the amino-terminal BRCT domain.
Structure-Function of the Tumor Suppressor BRCA1
TLDR
This mini-review examines the structure-function relationships of the BRCA1 protein and the relevance to cancer progression.
BRCA1 Tumor Suppression Depends on BRCT Phosphoprotein Binding, But Not Its E3 Ligase Activity
TLDR
It is found that a mutant Brca1 prevents tumor formation to the same degree as does wild-type Brca 1 in three different genetically engineered mouse (GEM) models of cancer.
Impact of BRCA1 BRCT Domain Missense Substitutions on Phosphopeptide Recognition
TLDR
The structures and peptide-binding activities of variants that affect the BRCA1 BRCT phosphopeptide- binding groove are probed and the role of Ser1655 in pSer recognition is illustrated.
BRCT domains: phosphopeptide binding and signaling modules.
TLDR
This review seeks to discuss the recent biochemical and structural data that have helped elucidate the molecular basis of BRCT domain function and BRCT-mediated interactions, with special emphasis on the role of phospho-specific interactions in key networks that regulate DNA repair.
ACCA phosphopeptide recognition by the BRCT repeats of BRCA1.
TLDR
It is demonstrated by immunoprecipitation of ACCA in cells, that the whole BRCA1 protein interacts with ACCA when phosphorylated on Ser1263, the most favourable candidate among six residues, for recognition by the BRCa1 BRCT repeats.
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References

SHOWING 1-10 OF 44 REFERENCES
Crystal structure of the BRCT repeat region from the breast cancer-associated protein BRCA1
TLDR
The structure provides a basis to predict the structural consequences of uncharacterized BRCA1 mutations and may represent a general mode of interaction between homologous domains within proteins that interact to regulate the cellular response to DNA damage.
Structural basis of phosphopeptide recognition by the BRCT domain of BRCA1
TLDR
Crystallographic and biochemical data suggest that the structural integrity of both binding sites is essential for peptide recognition, and the diminished peptide-binding capacity observed for cancer-associated BRCA1-BRCT variants may explain the enhanced cancer risks associated with these mutations.
Structural Consequences of a Cancer-causing BRCA1-BRCT Missense Mutation*
TLDR
Destabilization and global unfolding of the mutated BRCT domain at physiological temperatures explain the pleiotropic molecular and genetic defects associated with the BRCA1-M1775R protein.
Characterisation of the BRCT domains of the breast cancer susceptibility gene product BRCA1.
TLDR
An important role is indicated for biophysical studies in assessing the significance of sequence variants and in determining how they cause disease in BRCA1-mediated tumour suppression.
From BRCA1 to RAP1: a widespread BRCT module closely associated with DNA repair
TLDR
Sequence analysis using hydrophobic cluster analysis reveals the presence of 50 copies of the BRCT domain in 23 different proteins, including, in addition to BRCA1, 53BP1 and RAD9, XRCC1, RAD4, Ect2, REV1, Crb2, RAP1, terminal deoxynucleotidyltransferases (TdT) and three eukaryotic DNA ligases.
BACH1, a Novel Helicase-like Protein, Interacts Directly with BRCA1 and Contributes to Its DNA Repair Function
TLDR
A BACH1 derivative, bearing a mutation in a residue that was essential for catalytic function in other helicases, interfered with normal double-strand break repair in a manner that was dependent on its BRCA1 binding function.
The BRCA1-associated protein BACH1 is a DNA helicase targeted by clinically relevant inactivating mutations.
TLDR
It is shown that BACH1 is both a DNA-dependent ATPase and a 5'-to-3' DNA helicase, and in two patients with early-onset breast cancer who carry distinct germline Bach1 coding sequence changes, the resulting proteins are defective in helicase activity, indicating that these sequence changes disrupt protein function.
Crystal structure of human 53BP1 BRCT domains bound to p53 tumour suppressor
TLDR
The crystal structure of the 53BP1BRCT tandem repeat in complex with the DNA‐binding domain of p53 shows that the BRCT tandem repeats pack together through a conserved interface that also involves the inter‐domain linker.
The BRCT Domain Is a Phospho-Protein Binding Domain
TLDR
It is shown that the BRCA1 BRCT domain directly interacts with phosphorylated BRCa1-Associated Carboxyl-terminal Helicase (BACH1) and this interaction 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.
BRCT Repeats As Phosphopeptide-Binding Modules Involved in Protein Targeting
TLDR
Findings provide a molecular basis for BRCTdomain function in the DNA damage response and may help to explain why the BRCA1 BRCT domain mutation Met1775 → Arg, which fails to bind phosphopeptides, predisposes women to breast and ovarian cancer.
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