The Bloom's syndrome helicase can promote the regression of a model replication fork.
Homozygous inactivation of BLM gives rise to Bloom's syndrome, a disorder associated with genomic instability and cancer predisposition. BLM encodes a member of the RecQ DNA helicase family that is required for the maintenance of genome stability and the suppression of sister-chromatid exchanges. BLM has been proposed to function in the rescue of replication forks that have collapsed or stalled as a result of encountering lesions that block fork progression. One proposed mechanism of fork rescue involves regression in which the nascent leading and lagging strands anneal to create a so-called "chicken foot" structure. Here we have developed an in vitro system for analysis of fork regression and show that BLM, but not Escherichia coli RecQ, can promote the regression of a model replication fork. BLM-mediated fork regression is ATP-dependent and occurs processively, generating regressed arms of >250 bp in length. These data establish the existence of a eukaryotic protein that could promote replication fork regression in vivo and suggest a novel pathway through which BLM might suppress genetic exchanges.
Ralf
Christine
C
Cancer Research UK Laboratories, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, United Kingdom.
Hickson
Ian D
ID
Wu
Leonard
L
D000251:Adenosine Triphosphatases / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D004265:DNA Helicases / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D004261:DNA Replication; D045566:DNA, Cruciform; D004278:DNA, Superhelical; D004926:Escherichia coli / Q000378:metabolism; D006720:Homozygote; D006801:Humans; D008954:Models, Biological; D008957:Models, Genetic; D053484:RecQ Helicases; D011995:Recombination, Genetic; D012854:Sister Chromatid Exchange
D045566:DNA, Cruciform; D004278:DNA, Superhelical; D000251:Adenosine Triphosphatases; C097151:Bloom syndrome protein; C506725:RECQL protein, human; C506724:RecQ protein, E coli; D004265:DNA Helicases; D053484:RecQ Helicases