RecA: Regulation and Mechanism of a Molecular Search Engine

Jason C. Bell, Stephen C. Kowalczykowski

Research output: Contribution to journalReview article

65 Scopus citations

Abstract

Homologous recombination maintains genomic integrity by repairing broken chromosomes. The broken chromosome is partially resected to produce single-stranded DNA (ssDNA) that is used to search for homologous double-stranded DNA (dsDNA). This homology driven 'search and rescue' is catalyzed by a class of DNA strand exchange proteins that are defined in relation to Escherichia coli RecA, which forms a filament on ssDNA. Here, we review the regulation of RecA filament assembly and the mechanism by which RecA quickly and efficiently searches for and identifies a unique homologous sequence among a vast excess of heterologous DNA. Given that RecA is the prototypic DNA strand exchange protein, its behavior affords insight into the actions of eukaryotic RAD51 orthologs and their regulators, BRCA2 and other tumor suppressors. Single molecule methods have yielded new insight into how RecA filaments form and find homologous DNA. RecA nucleation and growth on SSB-coated ssDNA is kinetically regulated by the RecFOR and RecOR complexes, which both microscopically and macroscopically alter the SSB-ssDNA nucleoprotein fiber. RecA finds homology through many random, weak, and transient interactions made in parallel and ignores very short regions of microhomology resulting in a reduction of both dimensionality and complexity.

Original languageEnglish (US)
Pages (from-to)491-507
Number of pages17
JournalTrends in Biochemical Sciences
Volume41
Issue number6
DOIs
StatePublished - Jun 1 2016

Keywords

  • Förster resonance energy transfer (FRET)
  • Homology search
  • RAD51
  • Recombination
  • Self-assembly
  • Single molecule imaging
  • Total internal reflection fluorescence (TIRF)

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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