UmuD and RecA Directly Modulate the Mutagenic Potential of the Y Family DNA Polymerase DinB

Veronica G. Godoy, Daniel F. Jarosz, Sharotka M. Simon, Alexej Abyzov, Valentin Ilyin, Graham C. Walker

Research output: Contribution to journalArticle

74 Citations (Scopus)

Abstract

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 UmuD2 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 UmuD2-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 UmuD2 may be responsible for managing the mutagenic potential of DinB orthologs throughout evolution.

Original languageEnglish (US)
Pages (from-to)1058-1070
Number of pages13
JournalMolecular Cell
Volume28
Issue number6
DOIs
StatePublished - Dec 28 2007
Externally publishedYes

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DNA-Directed DNA Polymerase
Rec A Recombinases
Proteins
Archaea
Eukaryota
Mutagenesis
DNA Damage
Catalytic Domain
Maintenance
Bacteria
Phenotype

Keywords

  • DNA
  • MICROBIO

ASJC Scopus subject areas

  • Molecular Biology

Cite this

UmuD and RecA Directly Modulate the Mutagenic Potential of the Y Family DNA Polymerase DinB. / Godoy, Veronica G.; Jarosz, Daniel F.; Simon, Sharotka M.; Abyzov, Alexej; Ilyin, Valentin; Walker, Graham C.

In: Molecular Cell, Vol. 28, No. 6, 28.12.2007, p. 1058-1070.

Research output: Contribution to journalArticle

Godoy, Veronica G. ; Jarosz, Daniel F. ; Simon, Sharotka M. ; Abyzov, Alexej ; Ilyin, Valentin ; Walker, Graham C. / UmuD and RecA Directly Modulate the Mutagenic Potential of the Y Family DNA Polymerase DinB. In: Molecular Cell. 2007 ; Vol. 28, No. 6. pp. 1058-1070.
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