Abstract
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.
Highlights
Cent strands, the longer lagging strand can provide a template for the prematurely terminated leading strand to be extended
These proteins are unrelated functionally, which suggests that multiple mechanisms may exist to promote fork regression that could be utilized under different circumstances of replication fork repair [11]
The family is named after the E. coli prototypical member RecQ, and members are defined by the presence of a conserved catalytic helicase domain [15]
Summary
Cent strands, the longer lagging strand can provide a template for the prematurely terminated leading strand to be extended. AvrII released ϳ45% of the label as a 36-bp fragment indicating EcoRI, BamHI, or AvrII to release the labeled linear fragments that that nearly half of the labeled forks in substrate RFII had under- were predicted to arise from digestion of the regressed arm
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