What is it about?
Crb2 is part of the signalling process in the DNA damage checkpoint. It is required to arrest the cell cycle to allow repair of DNA damage. Crb2 contains 2 BRCT domains. Here we have analysed their structure and shown by mutating a number of key amino acids, that the phospho-protein binding site is required for checkpoint activation, while the inter-BRCT linker is required for processing of DNA damage
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Why is it important?
Crb2 is a good model for the mammalian 53BP1 protein. Thus information gained here may help us to gain a better understanding of the function of 53BP1 and its role in the DNA damage response.
Perspectives
This work follows on from previous work in our lab (Dore et al 2003, and Willson et al 1997). Here we have analysed the structure of the BRCT domains of CRb2, and using site-directed mutagenesis have identified a number of separation of function mutations. These mutations affect either DNA damage checkpoint activation or homologous recombination. Of particular interest is the fact that mutations within the phospho-protein binding site are highly sensitive to DNA damage and are defective in activation of the checkpoint.
Dr Felicity Z Watts
University of Sussex
Read the Original
This page is a summary of: Structural and functional analysis of the Crb2-BRCT2 domain reveals distinct roles in checkpoint signaling and DNA damage repair, Genes & Development, August 2008, Cold Spring Harbor Laboratory Press,
DOI: 10.1101/gad.472808.
You can read the full text:
Resources
Isolation and characterization of the Schizosaccharomyces pombe rhp9 gene: a gene required for the DNA damage checkpoint but not the replication checkpoint
Our initial characterisation of the Crb2 gene
Expression, purification and preliminary X-ray analysis of the BRCT domain from Rhp9/Crb2
Our preliminary crystallisation studies on the Crb2 BRCT domains
Linking up and interacting with BRCT domains
A review from our lab on BRCT domains
Contributors
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