The Rad51 paralog complex Rad55-Rad57 acts as a molecular chaperone during homologous recombination

Upasana Roy, Youngho Kwon, Lea Marie, Lorraine Symington, Patrick Sung, Michael Lisby, Eric C. Greene

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Homologous recombination (HR) is essential for maintenance of genome integrity. Rad51 paralogs fulfill a conserved but undefined role in HR, and their mutations are associated with increased cancer risk in humans. Here, we use single-molecule imaging to reveal that the Saccharomyces cerevisiae Rad51 paralog complex Rad55-Rad57 promotes assembly of Rad51 recombinase filament through transient interactions, providing evidence that it acts like a classical molecular chaperone. Srs2 is an ATP-dependent anti-recombinase that downregulates HR by actively dismantling Rad51 filaments. Contrary to the current model, we find that Rad55-Rad57 does not physically block the movement of Srs2. Instead, Rad55-Rad57 promotes rapid re-assembly of Rad51 filaments after their disruption by Srs2. Our findings support a model in which Rad51 is in flux between free and single-stranded DNA (ssDNA)-bound states, the rate of which is controlled dynamically though the opposing actions of Rad55-Rad57 and Srs2. Roy et al. present a single-molecule analysis of the Rad51 paralog complex Rad55-Rad57. They show that Rad55-Rad57 binds transiently to Rad51-ssDNA to promote Rad51 filament assembly but then dissociates quickly as the filaments mature. They further demonstrate that Rad55-Rad57 does not block the translocase Srs2.

Original languageEnglish (US)
Pages (from-to)1043-1057.e8
JournalMolecular Cell
Volume81
Issue number5
DOIs
StatePublished - Mar 4 2021

Keywords

  • DNA curtains
  • DNA repair
  • Rad51
  • Rad51 paralogs
  • Rad55-Rad57
  • Srs2
  • homologous recombination
  • single-molecule

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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