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<p>Meiotic crossover formation is critical for generating viable gametes and enhancing genetic diversity. The helicase Mer3 (HFM1 in humans) is a highly conserved factor essential for promoting crossovers and ensuring their proper distribution. Here, we identify replication protein A (RPA) as a direct interactor of budding yeast Mer3. We demonstrate that this interaction is conserved between human HFM1 and RPA. Cross-linking mass spectrometry and structural modelling with AlphaFold2 reveal a conserved and specific Mer3-RPA interface. Single-molecule magnetic tweezers assays demonstrate that direct RPA interaction is required for Mer3 helicase processivity under conditions of low DNA tension. Consistently, a <i>mer3</i> mutant deficient in RPA binding exhibits reduced crossover frequencies and accumulates unresolved recombination intermediates during budding yeast meiosis. Via genome-wide localisation experiments, we link this effect to weakened recruitment of the mer3 mutant to double-strand break sites. Our findings provide mechanistic insights into coordination of meiotic recombination by the Mer3 helicase through interactions with the canonical DNA repair machinery, highlighting a conserved mechanism underlying crossover control during sexual reproduction.</p>

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RPA directly stimulates Mer3 helicase processivity to ensure normal crossover formation in meiosis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月18日

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  • Veronika Altmannova,
  • Lucija Orlić,
  • Carolina Carrasco,
  • Céline Adam,
  • Clara Aicart-Ramos,
  • Dario Guerrini,
  • Petra Janning,
  • Valérie Borde,
  • Joao Matos,
  • Fernando Moreno-Herrero,
  • John R. Weir

摘要

Meiotic crossover formation is critical for generating viable gametes and enhancing genetic diversity. The helicase Mer3 (HFM1 in humans) is a highly conserved factor essential for promoting crossovers and ensuring their proper distribution. Here, we identify replication protein A (RPA) as a direct interactor of budding yeast Mer3. We demonstrate that this interaction is conserved between human HFM1 and RPA. Cross-linking mass spectrometry and structural modelling with AlphaFold2 reveal a conserved and specific Mer3-RPA interface. Single-molecule magnetic tweezers assays demonstrate that direct RPA interaction is required for Mer3 helicase processivity under conditions of low DNA tension. Consistently, a mer3 mutant deficient in RPA binding exhibits reduced crossover frequencies and accumulates unresolved recombination intermediates during budding yeast meiosis. Via genome-wide localisation experiments, we link this effect to weakened recruitment of the mer3 mutant to double-strand break sites. Our findings provide mechanistic insights into coordination of meiotic recombination by the Mer3 helicase through interactions with the canonical DNA repair machinery, highlighting a conserved mechanism underlying crossover control during sexual reproduction.