Abstract：
:The Chk2 Ser/Thr kinase plays crucial, evolutionarily conserved roles in cellular responses to DNA damage. Identification of two pro-oncogenic mutations within the Chk2 FHA domain has highlighted its importance for Chk2 function in checkpoint activation. The X-ray structure of the Chk2 FHA domain in complex with an in vitro selected phosphopeptide motif reveals the determinants of binding specificity and shows that both mutations are remote from the peptide binding site. We show that the Chk2 FHA domain mediates ATM-dependent Chk2 phosphorylation and targeting of Chk2 to in vivo binding partners such as BRCA1 through either or both of two structurally distinct mechanisms. Although phospho-dependent binding is important for Chk2 activity, previously uncharacterized phospho-independent FHA domain interactions appear to be the primary target of oncogenic lesions.
journal_name
Mol Celljournal_title
Molecular cellauthors
Li J,Williams BL,Haire LF,Goldberg M,Wilker E,Durocher D,Yaffe MB,Jackson SP,Smerdon SJdoi
10.1016/s1097-2765(02)00527-0subject
Has Abstractpub_date
2002-05-01 00:00:00pages
1045-54issue
5eissn
1097-2765issn
1097-4164pii
S1097-2765(02)00527-0journal_volume
9pub_type
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