Escherichia coli RarA commits cells to post‐replication repair pathways by facilitating replisome skipping

Abstract

Members of the highly conserved RarA/Mgs1/WRNIP1 protein family have been implicated in the maintenance of genomic stability, but their exact functions remain unknown. Loss of one of these proteins rarely results in an altered phenotype, but a knockout mutation in genes encoding proteins of this family in tandem with the loss of other DNA metabolism functions can adversely affect cell survival. We hypothesize that the RarA protein of E. coli commits the cell to post‐replication repair pathways, namely translesion DNA synthesis (TLS) and daughter strand gap synthesis. RarA overexpression is toxic to the cell and knocking out DNA Polymerase IV and DNA Polymerase V, TLS‐competent polymerases, alleviates this toxicity. Furthermore, the presence of RarA induces sensitivity in cells lacking TLS polymerases to the DNA‐damaging agents nitrofurazone (NFZ) and 4‐nitroquinoline‐1‐oxide (4‐NQO). Deletion of RarA suppresses DNA Polymerase IV mediated sensitivity to NFZ and 4‐NQO. These data suggest that RarA can promote rapid replisome progress by committing cells to using post‐replication repair pathways and blocking access to other repair pathways when the replisome encounters certain types of lesions.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.