• Reference Type: Journal Article | Research Support, Non-U.S. Gov't
  Dion V, et al. (2012) Increased mobility of double-strand breaks requires Mec1, Rad9 and the homologous recombination machinery. Nat Cell Biol 14(5):502-9 PMID: 22484486
  • SGD Paper
  • DOI full text
  • PubMed

  Chromatin mobility is thought to facilitate homology search during homologous recombination and to shift damage either towards or away from specialized repair compartments. However, unconstrained mobility of double-strand breaks could also promote deleterious chromosomal translocations. Here we use live time-lapse fluorescence microscopy to track the mobility of damaged DNA in budding yeast. We found that a Rad52-YFP focus formed at an irreparable double-strand break moves in a larger subnuclear volume than the undamaged locus. In contrast, Rad52-YFP bound at damage arising from a protein-DNA adduct shows no increase in movement. Mutant analysis shows that enhanced double-strand-break mobility requires Rad51, the ATPase activity of Rad54, the ATR homologue Mec1 and the DNA-damage-response mediator Rad9. Consistent with a role for movement in the homology-search step of homologous recombination, we show that recombination intermediates take longer to form in cells lacking Rad9.

• Reference Type: Journal Article | Research Support, N.I.H., Extramural | Research Support, Non-U.S. Gov't
  Miné-Hattab J and Rothstein R (2012) Increased chromosome mobility facilitates homology search during recombination. Nat Cell Biol 14(5):510-7 PMID: 22484485
  • SGD Paper
  • DOI full text
  • PubMed

  Homologous recombination, an essential process for preserving genomic integrity, uses intact homologous sequences to repair broken chromosomes. To explore the mechanism of homologous pairing in vivo, we tagged two homologous loci in diploid yeast Saccharomyces cerevisiae cells and investigated their dynamic organization in the absence and presence of DNA damage. When neither locus is damaged, homologous loci occupy largely separate regions, exploring only 2.7% of the nuclear volume. Following the induction of a double-strand break, homologous loci co-localize ten times more often. The mobility of the cut chromosome markedly increases, allowing it to explore a nuclear volume that is more than ten times larger. Interestingly, the mobility of uncut chromosomes also increases, allowing them to explore a four times larger volume. We propose a model for homology search in which increased chromosome mobility facilitates homologous pairing. Finally, we find that the increase in DNA dynamics is dependent on early steps of homologous recombination.

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