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

Publication ,  Journal Article
Nimonkar, AV; Ozsoy, AZ; Genschel, J; Modrich, P; Kowalczykowski, SC
Published in: Proc Natl Acad Sci U S A
November 4, 2008

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.

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Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

November 4, 2008

Volume

105

Issue

44

Start / End Page

16906 / 16911

Location

United States

Related Subject Headings

  • Replication Protein A
  • Recombination, Genetic
  • RecQ Helicases
  • Rad51 Recombinase
  • Humans
  • Exodeoxyribonucleases
  • DNA Repair Enzymes
  • DNA Repair
  • DNA Helicases
  • DNA Breaks, Double-Stranded
 

Citation

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Nimonkar, A. V., Ozsoy, A. Z., Genschel, J., Modrich, P., & Kowalczykowski, S. C. (2008). Human exonuclease 1 and BLM helicase interact to resect DNA and initiate DNA repair. Proc Natl Acad Sci U S A, 105(44), 16906–16911. https://doi.org/10.1073/pnas.0809380105
Nimonkar, Amitabh V., A Zeynep Ozsoy, Jochen Genschel, Paul Modrich, and Stephen C. Kowalczykowski. “Human exonuclease 1 and BLM helicase interact to resect DNA and initiate DNA repair.Proc Natl Acad Sci U S A 105, no. 44 (November 4, 2008): 16906–11. https://doi.org/10.1073/pnas.0809380105.
Nimonkar AV, Ozsoy AZ, Genschel J, Modrich P, Kowalczykowski SC. Human exonuclease 1 and BLM helicase interact to resect DNA and initiate DNA repair. Proc Natl Acad Sci U S A. 2008 Nov 4;105(44):16906–11.
Nimonkar, Amitabh V., et al. “Human exonuclease 1 and BLM helicase interact to resect DNA and initiate DNA repair.Proc Natl Acad Sci U S A, vol. 105, no. 44, Nov. 2008, pp. 16906–11. Pubmed, doi:10.1073/pnas.0809380105.
Nimonkar AV, Ozsoy AZ, Genschel J, Modrich P, Kowalczykowski SC. Human exonuclease 1 and BLM helicase interact to resect DNA and initiate DNA repair. Proc Natl Acad Sci U S A. 2008 Nov 4;105(44):16906–16911.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

November 4, 2008

Volume

105

Issue

44

Start / End Page

16906 / 16911

Location

United States

Related Subject Headings

  • Replication Protein A
  • Recombination, Genetic
  • RecQ Helicases
  • Rad51 Recombinase
  • Humans
  • Exodeoxyribonucleases
  • DNA Repair Enzymes
  • DNA Repair
  • DNA Helicases
  • DNA Breaks, Double-Stranded