Human exonuclease 1 and BLM helicase interact to resect DNA and initiate DNA repair.

Published

Journal Article

The error-free repair of double-stranded DNA breaks by homologous recombination requires processing of broken ends. These processed ends are substrates for assembly of DNA strand exchange proteins that mediate DNA strand invasion. Here, we establish that human BLM helicase, a member of the RecQ family, stimulates the nucleolytic activity of human exonuclease 1 (hExo1), a 5'-->3' double-stranded DNA exonuclease. The stimulation is specific because other RecQ homologs fail to stimulate hExo1. Stimulation of DNA resection by hExo1 is independent of BLM helicase activity and is, instead, mediated by an interaction between the 2 proteins. Finally, we show that DNA ends resected by hExo1 and BLM are used by human Rad51, but not its yeast or bacterial counterparts, to promote homologous DNA pairing. This in vitro system recapitulates initial steps of homologous recombination and provides biochemical evidence for a role of BLM and Exo1 in the initiation of recombinational DNA repair.

Full Text

Duke Authors

Cited Authors

  • Nimonkar, AV; Ozsoy, AZ; Genschel, J; Modrich, P; Kowalczykowski, SC

Published Date

  • November 4, 2008

Published In

Volume / Issue

  • 105 / 44

Start / End Page

  • 16906 - 16911

PubMed ID

  • 18971343

Pubmed Central ID

  • 18971343

Electronic International Standard Serial Number (EISSN)

  • 1091-6490

Digital Object Identifier (DOI)

  • 10.1073/pnas.0809380105

Language

  • eng

Conference Location

  • United States