Meiosis reduces ploidy through two rounds of chromosome segregation preceded by one round of DNA replication. In meiosis I, homologous chromosomes segregate, while in meiosis II, sister chromatids separate from each other. Topoisomerase II (Topo II) is a conserved enzyme that alters DNA structure by introducing transient double-strand breaks. During mitosis, Topo II relieves topological stress associated with unwinding DNA during replication, recombination, and sister chromatid segregation. Topo II also plays a role in maintaining mitotic chromosome structure. However, the role and regulation of Topo II during meiosis is not well-defined. Previously, we found an allele of Topo II, , disrupts homologous chromosome segregation during meiosis I of spermatogenesis. In a genetic screen, we identified different point mutations in 5′-tyrosyl-DNA phosphodiesterase two (Tdp2, ) that suppress embryonic lethality. Tdp2 removes trapped Top-2-DNA complexes. The suppressing mutations rescue embryonic lethality, ameliorate chromosome segregation defects, and restore TOP-2 protein levels of . Here, we show that both TOP-2 and TDPT-1 are expressed in germ line nuclei but occupy different compartments until late meiotic prophase. We also demonstrate that suppression is due to loss of function of the protein and that the mutations do not have a phenotype independent of in meiosis. Lastly, we found that the suppressing mutations either impair the phosphodiesterase activity, affect the stability of TDPT-1, or disrupt protein interactions. This suggests that the WT TDPT-1 protein is inhibiting chromosome biological functions of an impaired TOP-2 during meiosis.

中文翻译：

---

酪氨酰 DNA 磷酸二酯酶 2 的突变抑制线虫精子发生过程中 top-2 诱导的染色体分离缺陷


减数分裂通过两轮染色体分离和一轮 DNA 复制来减少倍性。在减数分裂 I 中，同源染色体分离，而在减数分裂 II 中，姐妹染色单体彼此分离。拓扑异构酶 II (Topo II) 是一种保守酶，可通过引入短暂的双链断裂来改变 DNA 结构。在有丝分裂过程中，Topo II 可以缓解复制、重组和姐妹染色单体分离过程中 DNA 解旋相关的拓扑应激。 Topo II 还在维持有丝分裂染色体结构中发挥作用。然而，Topo II 在减数分裂过程中的作用和调节尚不明确。此前，我们发现 Topo II 的等位基因 ，在精子发生减数分裂 I 期间破坏同源染色体分离。在基因筛选中，我们发现了 5'-酪氨酰 DNA 磷酸二酯酶二 (Tdp2, ) 中不同的点突变可抑制胚胎致死率。 Tdp2 去除捕获的 Top-2-DNA 复合物。抑制突变可挽救胚胎致死性、改善染色体分离缺陷并恢复 TOP-2 蛋白水平。在这里，我们发现 TOP-2 和 TDPT-1 均在种系细胞核中表达，但直到减数分裂前期晚期才占据不同的区室。我们还证明抑制是由于蛋白质功能丧失造成的，并且突变不具有独立于减数分裂的表型。最后，我们发现抑制突变要么损害磷酸二酯酶活性，影响 TDPT-1 的稳定性，要么破坏蛋白质相互作用。这表明 WT TDPT-1 蛋白在减数分裂过程中抑制受损 TOP-2 的染色体生物学功能。