Biochemical characterization of RecA variants that contribute to extreme resistance to ionizing radiation

DNA Repair (Amst). 2015 Feb:26:30-43. doi: 10.1016/j.dnarep.2014.12.001. Epub 2014 Dec 9.

Abstract

Among strains of Escherichia coli that have evolved to survive extreme exposure to ionizing radiation, mutations in the recA gene are prominent and contribute substantially to the acquired phenotype. Changes at amino acid residue 276, D276A and D276N, occur repeatedly and in separate evolved populations. RecA D276A and RecA D276N exhibit unique adaptations to an environment that can require the repair of hundreds of double strand breaks. These two RecA protein variants (a) exhibit a faster rate of filament nucleation on DNA, as well as a slower extension under at least some conditions, leading potentially to a distribution of the protein among a higher number of shorter filaments, (b) promote DNA strand exchange more efficiently in the context of a shorter filament, and (c) are markedly less inhibited by ADP. These adaptations potentially allow RecA protein to address larger numbers of double strand DNA breaks in an environment where ADP concentrations are higher due to a compromised cellular metabolism.

Keywords: DNA repair; Double strand break repair; Evolution; Radiation resistance; RecA protein.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Diphosphate / metabolism
  • Adenosine Triphosphate / metabolism
  • DNA, Bacterial / metabolism
  • DNA, Single-Stranded / metabolism
  • DNA-Binding Proteins / antagonists & inhibitors
  • DNA-Binding Proteins / metabolism
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Escherichia coli Proteins / antagonists & inhibitors
  • Escherichia coli Proteins / genetics*
  • Escherichia coli Proteins / metabolism
  • Mutation*
  • Radiation Tolerance / genetics*
  • Radiation, Ionizing
  • Rec A Recombinases / antagonists & inhibitors
  • Rec A Recombinases / genetics*
  • Rec A Recombinases / metabolism
  • Recombinational DNA Repair / genetics*
  • Recombinational DNA Repair / physiology

Substances

  • DNA, Bacterial
  • DNA, Single-Stranded
  • DNA-Binding Proteins
  • Escherichia coli Proteins
  • Adenosine Diphosphate
  • Adenosine Triphosphate
  • Rec A Recombinases