A functional interaction of Ku with Werner exonuclease facilitates digestion of damaged DNA

David K. Orren, Amrita Machwe, Parimal Karmakar, Jason Piotrowski, Marcus P. Cooper, Vilhelm A. Bohr

Research output: Contribution to journalArticlepeer-review

81 Scopus citations

Abstract

Werner syndrome (WS) is a premature aging disorder where the affected individuals appear much older than their chronological age. The single gene that is defective in WS encodes a protein (WRN) that has ATPase, helicase and 3′→5′ exonuclease activities. Our laboratory has recently uncovered a physical and functional interaction between WRN and the Ku heterodimer complex that functions in double-strand break repair and V(D)J recombination. Importantly, Ku specifically stimulates the exonuclease activity of WRN. We now report that Ku enables the Werner exonuclease to digest through regions of DNA containing 8-oxoadenine and 8-oxoguanine modifications, lesions that have previously been shown to block the exonuclease activity of WRN alone. These results indicate that Ku significantly alters the exonuclease function of WRN and suggest that the two proteins function concomitantly in a DNA damage processing pathway. In support of this notion we also observed co-localization of WRN and Ku, particularly after DNA damaging treatments.

Original languageEnglish
Pages (from-to)1926-1934
Number of pages9
JournalNucleic Acids Research
Volume29
Issue number9
DOIs
StatePublished - May 1 2001

ASJC Scopus subject areas

  • Genetics

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