UmuD and RecA directly modulate the mutagenic potential of the Y family DNA polymerase DinB.
DinB is the only translesion Y family DNA polymerase conserved among bacteria, archaea, and eukaryotes. DinB and its orthologs possess a specialized lesion bypass function but also display potentially deleterious -1 frameshift mutagenic phenotypes when overproduced. We show that the DNA damage-inducible proteins UmuD(2) and RecA act in concert to modulate this mutagenic activity. Structural modeling suggests that the relatively open active site of DinB is enclosed by interaction with these proteins, thereby preventing the template bulging responsible for -1 frameshift mutagenesis. Intriguingly, residues that define the UmuD(2)-interacting surface on DinB statistically covary throughout evolution, suggesting a driving force for the maintenance of a regulatory protein-protein interaction at this site. Together, these observations indicate that proteins like RecA and UmuD(2) may be responsible for managing the mutagenic potential of DinB orthologs throughout evolution.
Godoy
Veronica G
VG
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Jarosz
Daniel F
DF
Simon
Sharotka M
SM
Abyzov
Alexej
A
Ilyin
Valentin
V
Walker
Graham C
GC
D000595:Amino Acid Sequence; D001665:Binding Sites / Q000235:genetics; D026481:Blotting, Far-Western; D019951:DNA Polymerase beta / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004259:DNA-Directed DNA Polymerase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009154:Mutation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011938:Rec A Recombinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
C094399:DinB protein, E coli; D029968:Escherichia coli Proteins; D011938:Rec A Recombinases; D019951:DNA Polymerase beta; D004259:DNA-Directed DNA Polymerase; C055218:UmuD protein, E coli