Novel pro- and anti-recombination activities of the Bloom's syndrome helicase.
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.
Bugreev
Dmitry V
DV
Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102, USA.
Yu
Xiong
X
Egelman
Edward H
EH
Mazin
Alexander V
AV
D000251:Adenosine Triphosphatases / Q000235:genetics* / Q000378:metabolism*; D001816:Bloom Syndrome / Q000235:genetics* / Q000378:metabolism*; D004265:DNA Helicases / Q000235:genetics* / Q000378:metabolism*; D004260:DNA Repair; D004277:DNA, Single-Stranded / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D066298:In Vitro Techniques; D046529:Microscopy, Electron, Transmission; D008954:Models, Biological; D051135:Rad51 Recombinase / Q000235:genetics / Q000378:metabolism; D053484:RecQ Helicases; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D011995:Recombination, Genetic
D004277:DNA, Single-Stranded; D011994:Recombinant Proteins; C495153:RAD51 protein, human; D051135:Rad51 Recombinase; D000251:Adenosine Triphosphatases; C097151:Bloom syndrome protein; D004265:DNA Helicases; D053484:RecQ Helicases