Pathological replication in cells lacking RecG DNA translocase.
Little is known about what happens when forks meet to complete DNA replication in any organism. In this study we present data suggesting that the collision of replication forks is a potential threat to genomic stability. We demonstrate that Escherichia coli cells lacking RecG helicase suffer major defects in chromosome replication following UV irradiation, and that this is associated with high levels of DNA synthesis initiated independently of the initiator protein DnaA. This UV-induced stable DNA replication is dependent on PriA helicase and continues long after UV-induced lesions have been excised. We suggest UV irradiation triggers the assembly of new replication forks, leading to multiple fork collisions outside the terminus area. Such collisions may generate branched DNAs that serve to establish further new forks, resulting in uncontrolled DNA amplification. We propose that RecG reduces the likelihood of this pathological cascade being set in motion by reducing initiation of replication at D- and R-loops, and other structures generated as a result of fork collisions. Our results shed light on why replication initiation in bacteria is limited to a single origin and why termination is carefully orchestrated to a single event within a restricted area each cell cycle.
Rudolph
Christian J
CJ
Institute of Genetics, University of Nottingham, Queen's Medical Centre, Nottingham, NG7 2UH, UK.
Upton
Amy L
AL
Harris
Lynda
L
Lloyd
Robert G
RG
D002455:Cell Division; D002876:Chromosomes, Bacterial / Q000235:genetics; D004249:DNA Damage; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D004261:DNA Replication / Q000528:radiation effects; D004269:DNA, Bacterial / Q000096:biosynthesis; D004926:Escherichia coli / Q000166:cytology / Q000235:genetics* / Q000378:metabolism / Q000528:radiation effects; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D014466:Ultraviolet Rays
D004269:DNA, Bacterial; D029968:Escherichia coli Proteins; C071446:RecG protein, E coli; C506743:priA protein, E coli; D004265:DNA Helicases