Structural mechanisms of DNA replication restart (352.2)

Abstract

Frequent collisions between cellular DNA replication complexes (replisomes) and obstacles such as damaged DNA or frozen protein complexes make DNA replication fork progression surprisingly sporadic. These collisions can lead to the ejection of replisomes prior to the completion of replication, which, if left unrepaired, results in bacterial cell death. As such, bacteria have evolved “DNA replication restart” mechanisms that reload replisomes onto abandoned DNA replication forks and D‐loop structures that result from recombinational DNA repair. In an early step in this process, the PriA DNA helicase binds to the fork/D‐loop structure in a structure‐specific (sequence‐independent) manner ‐ this DNA‐bound form of PriA then mediates assembly of the replication restart primosome, which reloads the replicative helicase (DnaB in E. coli). We have recently determined the X‐ray crystal structure of a bacterial PriA, which reveals a core helicase domain surrounded by auxiliary DNA‐binding domains that appear to be poised for specific binding of branched DNA structures. Mechanistic insights from this structure and others will be highlighted in my talk.