Novel pro- and anti-recombination activities of the Bloom's syndrome helicase

Dmitry V. Bugreev, Xiong Yu, Edward H. Egelman, Alexander V. Mazin

Research output: Contribution to journalArticlepeer-review

237 Scopus citations

Abstract

Bloom's syndrome (BS) is an autosomal recessive disorder characterized by a strong cancer predisposition. The defining feature of BS is extreme genome instability. The gene mutated in Bloom's syndrome, BLM, encodes a DNA helicase (BLM) of the RecQ family. BLM plays a role in homologous recombination; however, its exact function remains controversial. Mutations in the BLM cause hyperrecombination between sister chromatids and homologous chromosomes, indicating an anti-recombination role. Conversely, other data show that BLM is required for recombination. It was previously shown that in vitro BLM helicase promotes disruption of recombination intermediates, regression of stalled replication forks, and dissolution of double Holliday junctions. Here, we demonstrate two novel activities of BLM: disruption of the Rad51-ssDNA (single-stranded DNA) filament, an active species that promotes homologous recombination, and stimulation of DNA repair synthesis. Using in vitro reconstitution reactions, we analyzed how different biochemical activities of BLM contribute to its functions in homologous recombination.

Original languageEnglish (US)
Pages (from-to)3085-3094
Number of pages10
JournalGenes and Development
Volume21
Issue number23
DOIs
StatePublished - Dec 1 2007
Externally publishedYes

Keywords

  • BLM helicase
  • Bloom's syndrome
  • Homologous recombination
  • Rad51
  • Rad54
  • RecQ

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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