Single-strand-specific exonucleases prevent frameshift mutagenesis by suppressing SOS induction and the action of DinB/DNA polymerase IV in growing cells.
Escherichia coli strains carrying null alleles of genes encoding single-strand-specific exonucleases ExoI and ExoVII display elevated frameshift mutation rates but not base substitution mutation rates. We characterized increased spontaneous frameshift mutation in ExoI- ExoVII- cells and report that some of this effect requires RecA, an inducible SOS DNA damage response, and the low-fidelity, SOS-induced DNA polymerase DinB/PolIV, which makes frameshift mutations preferentially. We also find that SOS is induced in ExoI- ExoVII- cells. The data imply a role for the single-stranded exonucleases in guarding the genome against mutagenesis by removing excess single-stranded DNA that, if left, leads to SOS induction and PolIV-dependent mutagenesis. Previous results implicated PolIV in E. coli mutagenesis specifically during starvation or antibiotic stresses. Our data imply that PolIV can also promote mutation in growing cells under genome stress due to excess single-stranded DNA.
Hersh
Megan N
MN
Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030-3411, USA.
Morales
Liza D
LD
Ross
Kimberly J
KJ
Rosenberg
Susan M
SM
D019951:DNA Polymerase beta / Q000378:metabolism*; D004926:Escherichia coli / Q000201:enzymology* / Q000235:genetics* / Q000254:growth & development; D029968:Escherichia coli Proteins / Q000378:metabolism*; D005090:Exodeoxyribonucleases / Q000235:genetics / Q000378:metabolism; D016368:Frameshift Mutation; D017353:Gene Deletion; D013014:SOS Response, Genetics
C094399:DinB protein, E coli; D029968:Escherichia coli Proteins; D019951:DNA Polymerase beta; D005090:Exodeoxyribonucleases; C028450:exodeoxyribonuclease I; C026870:exodeoxyribonuclease VII