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

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.

journal_name

Genes Dev

journal_title

Genes & development

authors

Bugreev DV,Yu X,Egelman EH,Mazin AV

doi

10.1101/gad.1609007

subject

Has Abstract

pub_date

2007-12-01 00:00:00

pages

3085-94

issue

23

eissn

0890-9369

issn

1549-5477

pii

gad.1609007

journal_volume

21

pub_type

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