Y-family DNA polymerases respond to DNA damage-independent inhibition of replication fork progression.
In Escherichia coli, the Y-family DNA polymerases Pol IV (DinB) and Pol V (UmuD2'C) enhance cell survival upon DNA damage by bypassing replication-blocking DNA lesions. We report a unique function for these polymerases when DNA replication fork progression is arrested not by exogenous DNA damage, but with hydroxyurea (HU), thereby inhibiting ribonucleotide reductase, and bringing about damage-independent DNA replication stalling. Remarkably, the umuC122::Tn5 allele of umuC, dinB, and certain forms of umuD gene products endow E. coli with the ability to withstand HU treatment (HUR). The catalytic activities of the UmuC122 and DinB proteins are both required for HUR. Moreover, the lethality brought about by such stalled replication forks in the wild-type derivatives appears to proceed through the toxin/antitoxin pairs mazEF and relBE. This novel function reveals a role for Y-family polymerases in enhancing cell survival under conditions of nucleotide starvation, in addition to their established functions in response to DNA damage.
Godoy
Veronica G
VG
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Jarosz
Daniel F
DF
Walker
Fabianne L
FL
Simmons
Lyle A
LA
Walker
Graham C
GC
D001427:Bacterial Toxins / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects / Q000502:physiology*; D004251:DNA Transposable Elements / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004259:DNA-Directed DNA Polymerase / Q000235:genetics / Q000378:metabolism*; D024881:Drug Resistance, Bacterial / Q000235:genetics; D004722:Endoribonucleases; D048168:Escherichia coli K12 / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D006918:Hydroxyurea / Q000494:pharmacology; D016254:Mutagenesis, Insertional / Q000379:methods; D051841:Transcription Factor RelB
D001427:Bacterial Toxins; D004251:DNA Transposable Elements; D004268:DNA-Binding Proteins; D004259:DNA-Directed DNA Polymerase; D004722:Endoribonucleases; D029968:Escherichia coli Proteins; D006918:Hydroxyurea; C094399:DinB protein, E coli; C422954:MazE protein, E coli; C422955:MazF protein, E coli; C465567:RelB protein, E coli; D051841:Transcription Factor RelB; C465566:RelE protein, E coli; C120926:DNA polymerase V, E coli