4.8 Article

Regulation of Hed1 and Rad54 binding during maturation of the meiosis-specific presynaptic complex

Journal

EMBO JOURNAL
Volume 37, Issue 7, Pages -

Publisher

WILEY
DOI: 10.15252/embj.201798728

Keywords

homologous recombination; meiosis; Rad51 recombinase; single-molecule imaging

Funding

  1. NIH [R35GM118026, RO1 ES007061]
  2. Danish Council for Independent Research
  3. Villum Foundation
  4. European Research Council [ERCStG 242905]
  5. Damon Runyon Cancer Research Foundation [DRG 2310-17]

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Most eukaryotes have two Rad51/RecA family recombinases, Rad51, which promotes recombination during mitotic double-strand break (DSB) repair, and the meiosis-specific recombinase Dmc1. During meiosis, the strand exchange activity of Rad51 is downregulated through interactions with the meiosis-specific protein Hed1, which helps ensure that strand exchange is driven by Dmc1 instead of Rad51. Hed1 acts by preventing Rad51 from interacting with Rad54, a cofactor required for promoting strand exchange during homologous recombination. However, we have a poor quantitative understanding of the regulatory interplay between these proteins. Here, we use real-time single-molecule imaging to probe how the Hed1- and Rad54-mediated regulatory network contributes to the identity of mitotic and meiotic presynaptic complexes. Based on our findings, we define a model in which kinetic competition between Hed1 and Rad54 helps define the functional identity of the presynaptic complex as cells undergo the transition from mitotic to meiotic repair.

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