Increased chromosomal mobility after DNA damage is controlled by interactions between the recombination machinery and the checkpoint

Genes Dev. 2018 Sep 1;32(17-18):1242-1251. doi: 10.1101/gad.317966.118.

Abstract

During homologous recombination, cells must coordinate repair, DNA damage checkpoint signaling, and movement of chromosomal loci to facilitate homology search. In Saccharomyces cerevisiae, increased movement of damaged loci (local mobility) and undamaged loci (global mobility) precedes homolog pairing in mitotic cells. How cells modulate chromosome mobility in response to DNA damage remains unclear. Here, we demonstrate that global chromosome mobility is regulated by the Rad51 recombinase and its mediator, Rad52. Surprisingly, rad51Δ rad52Δ cells display checkpoint-dependent constitutively increased mobility, indicating that a regulatory circuit exists between recombination and checkpoint machineries to govern chromosomal mobility. We found that the requirement for Rad51 in this circuit is distinct from its role in recombination and that interaction with Rad52 is necessary to alleviate inhibition imposed by mediator recruitment to ssDNA. Thus, interplay between recombination factors and the checkpoint restricts increased mobility until recombination proteins are assembled at damaged sites.

Keywords: DNA damage checkpoint signaling; DNA repair; chromosome mobility; homologous recombination; homology search.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Chromosomes, Fungal / metabolism*
  • DNA Damage*
  • Homologous Recombination*
  • Mutation
  • Rad51 Recombinase / genetics
  • Rad51 Recombinase / physiology*
  • Rad52 DNA Repair and Recombination Protein / genetics
  • Rad52 DNA Repair and Recombination Protein / physiology*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / physiology*

Substances

  • RAD52 protein, S cerevisiae
  • Rad52 DNA Repair and Recombination Protein
  • Saccharomyces cerevisiae Proteins
  • RAD51 protein, S cerevisiae
  • Rad51 Recombinase