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Novel pro- and anti-recombination activities of the Bloom's syndrome helicase
Journal article   Open access   Peer reviewed

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

Dmitry V Bugreev, Xiong Yu, Edward H Egelman and Alexander V Mazin
Genes & development, v 21(23), pp 3085-3094
01 Dec 2007
PMID: 18003860
url
https://doi.org/10.1101/gad.1609007View
Published, Version of Record (VoR) Open

Abstract

Rad51 Recombinase - metabolism Recombinant Proteins - metabolism Microscopy, Electron, Transmission DNA, Single-Stranded - ultrastructure Rad51 Recombinase - genetics DNA, Single-Stranded - metabolism Humans Adenosine Triphosphatases - metabolism Bloom Syndrome - metabolism Recombinant Proteins - genetics Bloom Syndrome - genetics DNA, Single-Stranded - chemistry DNA, Single-Stranded - genetics DNA Helicases - metabolism RecQ Helicases Models, Biological Recombination, Genetic DNA Repair Adenosine Triphosphatases - genetics In Vitro Techniques DNA Helicases - genetics
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.

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Collaboration types
Domestic collaboration
International collaboration
Web of Science research areas
Cell Biology
Developmental Biology
Genetics & Heredity
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