Research Summary

Chromosome cohesion mediated regulation of Homologous Recombination process in E. coli

Homologous recombination (HR) is the major source of antibiotic-resistant gene expansion in pathogenic microbes. HR processes are conserved in all organisms, playing an important role in genomic maintenance during repair of DNA double strand breaks (DSBs) and reactivation of stalled replication fork. However, HR can also induce genomic instability via gene conversion, crossing over and mutation incorporation (under stress), thereby resulting in gene translocations, deletions, amplifications, inversions and loss of heterozygosity. Therefore, HR plays a pivotal role in maintaining the equilibrium between genomic integrity and genetic diversity. Although HR is an extensively studied process, it remains unclear how this equilibrium is regulated during DNA repair. Recent data including our own suggested that chromosome cohesion is an evolutionary conserved process (Fig.1.) and bacteria may also utilize a cohesion dependent mechanism for DSB repair. Therefore, the E. coli provides a highly tractable and mutable model to test the role of cohesion in HR dependent DSB repair.

 

Figure Legend: Cohesion mediated segregation of E. coli chromosome: Positive supercoils migrate behind the replisome, entwining newly replicated sister regions. Resolution of precatenanes by Topo IV (green) is delayed by SeqA (red), which binds to hemimethylated DNA tracts behind the fork. Five to ten minutes after fork passage, DNA is remethylated by Dam (blue), releasing SeqA, and allowing Topo IV to resolve inter-sister links.