In meiosis, DNA double strand break (DSB) formation by Spo11 initiates recombination and enables chromosome segregation. Numerous factors are required for Spo11 activity, and couple the DSB machinery to the development of a meiosis-specific 'axis-tethered loop' chromosome organization. Through in vitro reconstitution and budding yeast genetics we here provide architectural insight into the DSB machinery by focussing on a foundational DSB factor, Mer2. We characterise the interaction of Mer2 with the histone reader Spp1, and show that Mer2 directly associates to nucleosomes, likely highlighting a contribution of Mer2 to tethering DSB factors to chromatin. We reveal the biochemical basis of Mer2 association with Hop1, a HORMA domain-containing chromosomal axis factor. Finally, we identify a conserved region within Mer2 crucial for DSB activity, and show that this region of Mer2 establishes an interaction with the DSB factor Mre11. In combination with previous work, we establish Mer2 as a keystone of the DSB machinery by bridging key protein complexes involved in the initiation of meiotic recombination.

中文翻译：

---

对 Mer2 作为减数分裂 DNA 断裂形成基石的作用的新机制见解

在减数分裂中，Spo11 形成的 DNA 双链断裂 (DSB) 启动重组并使染色体分离。Spo11 活动需要许多因素，并将 DSB 机制与减数分裂特定的“轴系链环”染色体组织的发展相结合。通过体外重组和出芽酵母遗传学，我们在这里通过关注基础 DSB 因子 Mer2 来提供对 DSB 机制的架构洞察。我们描述了 Mer2 与组蛋白阅读器 Spp1 的相互作用，并表明 Mer2 直接与核小体相关联，这可能突出了 Mer2 对将 DSB 因子束缚到染色质的贡献。我们揭示了 Mer2 与 Hop1 关联的生化基础，Hop1 是一种含有 HORMA 结构域的染色体轴因子。最后，我们在 Mer2 中鉴定了一个对 DSB 活性至关重要的保守区域，并表明 Mer2 的这个区域与 DSB 因子 Mre11 建立了相互作用。结合以前的工作，我们通过桥接参与减数分裂重组启动的关键蛋白质复合物，将 Mer2 确立为 DSB 机制的基石。