Center for Reproductive Medicine, Cheeloo College of Medicine, State Key Laboratory of Microbial Technology, Shandong University, China.
National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, Shandong 250012, China.
Nucleic Acids Res. 2022 Oct 14;50(18):10418-10435. doi: 10.1093/nar/gkac786.
Interference exists ubiquitously in many biological processes. Crossover interference patterns meiotic crossovers, which are required for faithful chromosome segregation and evolutionary adaption. However, what the interference signal is and how it is generated and regulated is unknown. We show that yeast top2 alleles which cannot bind or cleave DNA accumulate a higher level of negative supercoils and show weaker interference. However, top2 alleles which cannot religate the cleaved DNA or release the religated DNA accumulate less negative supercoils and show stronger interference. Moreover, the level of negative supercoils is negatively correlated with crossover interference strength. Furthermore, negative supercoils preferentially enrich at crossover-associated Zip3 regions before the formation of meiotic DNA double-strand breaks, and regions with more negative supercoils tend to have more Zip3. Additionally, the strength of crossover interference and homeostasis change coordinately in mutants. These findings suggest that the accumulation and relief of negative supercoils pattern meiotic crossovers.
干扰普遍存在于许多生物过程中。交叉干扰模式减数分裂交叉，这是为了忠实的染色体分离和进化适应。然而，干扰信号是什么，以及它是如何产生和调节的还不清楚。我们表明，不能结合或切割 DNA 的酵母 top2 等位基因积累了更高水平的负超螺旋，并表现出较弱的干扰。然而，不能重新连接切割 DNA 或释放重新连接 DNA 的 top2 等位基因积累较少的负超螺旋，并表现出更强的干扰。此外，负超螺旋的水平与交叉干扰强度呈负相关。此外，负超螺旋优先富集在减数分裂 DNA 双链断裂形成之前的与交叉相关的 Zip3 区域，并且具有更多负超螺旋的区域往往具有更多的 Zip3。此外，交叉干扰的强度和内稳态在突变体中协调变化。这些发现表明，负超螺旋的积累和缓解模式减数分裂交叉。
