Institute for Protein Research, Osaka University, Suita, Osaka 565-0871, Japan.
Graduate School of Science, Osaka University, Suita, Osaka 565-0871, Japan.
Int J Mol Sci. 2020 Apr 12;21(8):2679. doi: 10.3390/ijms21082679.
Homologous recombination is essential for chromosome segregation during meiosis I. Meiotic recombination is initiated by the introduction of double-strand breaks (DSBs) at specific genomic locations called hotspots, which are catalyzed by Spo11 and its partners. DSB hotspots during meiosis are marked with Set1-mediated histone H3K4 methylation. The Spo11 partner complex, Rec114-Mer2-Mei4, essential for the DSB formation, localizes to the chromosome axes. For efficient DSB formation, a hotspot with histone H3K4 methylation on the chromatin loops is tethered to the chromosome axis through the H3K4 methylation reader protein, Spp1, on the axes, which interacts with Mer2. In this study, we found genetic interaction of mutants in a histone modification protein complex called PAF1C with the and in the DSB formation in budding yeast . Namely, the mutations and showed synthetic defects in meiotic DSB formation only when combined with a wild-type-like tagged allele of either the or . The synthetic defect of the tagged allele in the DSB formation was seen also with the , but not with deletion. These results suggest a novel role of histone modification machinery in DSB formation during meiosis, which is independent of Spp1-mediated loop-axis tethering.
同源重组对于减数分裂 I 期间的染色体分离至关重要。减数分裂重组是由特定基因组位置（称为热点）的双链断裂（DSB）引发的，这些热点由 Spo11 及其伴侣催化。减数分裂中的 DSB 热点用 Set1 介导的组蛋白 H3K4 甲基化标记。对于 DSB 的形成至关重要的 Spo11 伴侣复合物 Rec114-Mer2-Mei4 定位于染色体轴上。为了实现有效的 DSB 形成，带有组蛋白 H3K4 甲基化的热点通过轴上的 H3K4 甲基化读取蛋白 Spp1 与染色体轴相连，该蛋白与 Mer2 相互作用。在这项研究中，我们发现称为 PAF1C 的组蛋白修饰蛋白复合物的突变体与 和 在芽殖酵母中的 DSB 形成中存在遗传相互作用。即，只有与 或 的野生型样标记等位基因组合时， 突变体 和 才会在减数分裂 DSB 形成中表现出合成缺陷。在 DSB 形成中，标记 等位基因的合成缺陷也见于 ，但不发生于 缺失。这些结果表明组蛋白修饰机制在减数分裂期间 DSB 形成中具有新的作用，这与 Spp1 介导的环轴连接无关。
