Presynaptic filament dynamics in homologous recombination and DNA repair

Jie Liu, Kirk T. Ehmsen, Wolf Dietrich Heyer, Scott W. Morrical

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Homologous recombination (HR) is an essential genome stability mechanism used for high-fidelity repair of DNA double-strand breaks and for the recovery of stalled or collapsed DNA replication forks. The crucial homology search and DNA strand exchange steps of HR are catalyzed by presynaptic filamentsâ€"helical filaments of a recombinase enzyme bound to single-stranded DNA (ssDNA). Presynaptic filaments are fundamentally dynamic structures, the assembly, catalytic turnover, and disassembly of which must be closely coordinated with other elements of the DNA recombination, repair, and replication machinery in order for genome maintenance functions to be effective. Here, we reviewed the major dynamic elements controlling the assembly, activity, and disassembly of presynaptic filaments; some intrinsic such as recombinase ATP-binding and hydrolytic activities, others extrinsic such as ssDNA-binding proteins, mediator proteins, and DNA motor proteins. We examined dynamic behavior on multiple levels, including atomic- and filament-level structural changes associated with ATP binding and hydrolysis as evidenced in crystal structures, as well as subunit binding and dissociation events driven by intrinsic and extrinsic factors. We examined the biochemical properties of recombination proteins from four model systems (T4 phage, Escherichia coli, Saccharomyces cerevisiae, and Homo sapiens), demonstrating how their properties are tailored for the context-specific requirements in these diverse species. We proposed that the presynaptic filament has evolved to rely on multiple external factors for increased multilevel regulation of HR processes in genomes with greater structural and sequence complexity.

Original languageEnglish (US)
Pages (from-to)240-270
Number of pages31
JournalCritical Reviews in Biochemistry and Molecular Biology
Volume46
Issue number3
DOIs
StatePublished - Jun 2011

Keywords

  • BRCA2
  • helicase
  • mediator proteins
  • Rad51
  • RecA
  • Recombinase
  • SSB
  • translocase

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry

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