Abstract
Aberrant DNA replication is a major source of the mutations and chromosomal rearrangements associated with pathological disorders. In bacteria, several different DNA lesions are repaired by homologous recombination, a process that involves sister chromatid pairing. Previous work in Escherichia coli has demonstrated that sister chromatid interactions (SCIs) mediated by topological links termed precatenanes, are controlled by topoisomerase IV. In the present work, we demonstrate that during the repair of mitomycin C-induced lesions, topological links are rapidly substituted by an SOS-induced sister chromatid cohesion process involving the RecN protein. The loss of SCIs and viability defects observed in the absence of RecN were compensated by alterations in topoisomerase IV, suggesting that the main role of RecN during DNA repair is to promote contacts between sister chromatids. RecN also modulates whole chromosome organization and RecA dynamics suggesting that SCIs significantly contribute to the repair of DNA double-strand breaks (DSBs).
Highlights
In every cell, DNA carries the genetic information making all life forms possible
We demonstrate that during the repair of mitomycin C-induced lesions, topological links are rapidly substituted by an SOS-induced sister chromatid cohesion process involving the RecN protein
If Gyrase is inhibited and the precatenanes are diffused behind the fork, why isn’t topoisomerase IV (Topo IV) action enough to release the topological links causing sister chromatid interactions (SCIs)? Could there be an excess of precatenanes that Topo IV is unable to handle? Are these precatenanes partly involved in the rescue of the recN viability? We can hypothesize that replication may be only partly arrested, moving gradually forward as the supercoils ahead of the fork diffuse behind
Summary
DNA carries the genetic information making all life forms possible. Maintaining genome integrity is essential to ensure faithful transmission of the genetic information to the generation. Using the site specific loxP recombination assay, they showed that the recombination frequency was drastically increased when the activity of Topo IV is impaired in a parEts or parCts mutant, suggesting that sister chromatids stay tightly bound together when Topo IV activity is inhibited These observations lead to a model where precatenanes form behind the replication fork, interlocking the newly replicated sister chromatids, keeping them cohesive for a period of time before the action of Topoisomerase IV allows their segregation. They observed that in a seqA mutant, the cohesion period of the gln locus dropped from 30 min to 12 min They propose that SeqA binds immediately behind the replication fork, on hemimethylated DNA, and on GATC sites, delaying precatenane removal by Topo IV. The amount of 1 loxP product versus the total amount of DNA gives the recombination frequency and the amount of sister chromatid interactions (Figure 1)
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