Journal Article

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

Genschel, Jochen, Kowalczykowski, Stephen C, Özsoy, A. Zeynep, Nimonkar, Amitabh V, Modrich, Paul

2008

Overview

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'[rightward arrow]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.

• Publisher: National Academy of Sciences,National Acad Sciences
• Subject: Adenosine Triphosphatases - metabolism / Biochemistry / Biological Sciences / Bloom syndrome / Chromosomes / Deoxyribonucleic acid / DNA / DNA - chemistry / DNA - metabolism / DNA assembly / DNA Breaks, Double-Stranded / DNA damage / DNA Helicases - chemistry / DNA Helicases - genetics / DNA Helicases - metabolism / DNA Repair / DNA Repair Enzymes - chemistry / DNA Repair Enzymes - metabolism / Exodeoxyribonucleases - chemistry / Exodeoxyribonucleases - metabolism / Gels / homologous recombination / Humans / Molecular interactions / Molecules / Proteins / Rad51 Recombinase - metabolism / Recombination, Genetic / RecQ Helicases - metabolism / Replication Protein A - metabolism / resection / Social interaction / Yeasts