Mechanism of DNA substrate recognition by the mammalian DNA repair enzyme, Polynucleotide Kinase.

ABSTRACT: Mammalian polynucleotide kinase (mPNK) is a critical DNA repair enzyme whose 5'-kinase and 3'-phoshatase activities function with poorly understood but striking specificity to restore 5'-phosphate/3'-hydroxyl termini at sites of DNA damage. Here we integrated site-directed mutagenesis and small-angle X-ray scattering (SAXS) combined with advanced computational approaches to characterize the conformational variability and DNA-binding properties of mPNK. The flexible attachment of the FHA domain to the catalytic segment, elucidated by SAXS, enables the interactions of mPNK with diverse DNA substrates and protein partners required for effective orchestration of DNA end repair. Point mutations surrounding the kinase active site identified two substrate recognition surfaces positioned to contac

SUBMITTER: Bernstein NK 

PROVIDER: S-EPMC2764422 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature