Persistent DNA-break potential near telomeres increases initiation of meiotic recombination on short chromosomes

Faithful meiotic chromosome inheritance and fertility relies on the stimulation of meiotic crossover recombination by potentially genotoxic DNA double-strand breaks (DSBs). To avoid excessive damage, feedback mechanisms down-regulate DSBs on chromosomes that have successfully initiated crossover repair. In Saccharomyces cerevisiae, this regulation requires the removal of the conserved DSB-promoting protein Hop1/HORMAD during chromosome synapsis. Here, we identify privileged end-adjacent regions (EARs) spanning roughly 100 Kb near all telomeres that escape DSB downregulation. These regions retain Hop1 and continue to break in pachynema despite normal synaptonemal complex deposition. Differential retention of Hop1 requires the disassemblase Pch2/TRIP13, which preferentially removes Hop1 from telomere-distant sequences, and is modulated by the histone deacetylase Sir2 and the nucleoporin Nup2. Importantly, the uniform size of EARs among chromosomes contributes to disproportionately high DSB and repair signals on short chromosomes in pachynema, suggesting that EARs partially underlie the curiously high recombination rate of short chromosomes. Grant ID: Research grant #6-FY16-208 Grant title: Meiotic segregation of small chromosomes Funding Source: March of Dimes Foundation Affiliation: NEW YORK UNIVERSITY Name: Andreas Hochwagen ChIP-seq analysis of Hop1, Red1, Zip1, pH2A, Mek1 and Rad51 in S. cerevisiae in meiosis. Each bedgraph file is the combined results from two biological replicates (each with a paired Input and ChIP sample). Please note that as processed data was generated from multiple samples, the corresponding processed data file is indicated in each sample description field.

减数分裂染色体的忠实遗传与生殖育性，依赖于具有潜在遗传毒性的DNA双链断裂（double-strand breaks, DSBs）对减数分裂交叉重组的诱导作用。为避免过度损伤，机体通过反馈机制对已成功启动交叉修复的染色体上的DSBs进行下调调控。在酿酒酵母（Saccharomyces cerevisiae）中，该调控过程需要在染色体联会阶段移除保守的促DSB蛋白Hop1/HORMAD。
本研究鉴定出位于所有端粒附近、跨度约100 kb的优先邻近末端区域（end-adjacent regions, EARs），此类区域可逃避DSB下调调控。尽管联会复合体的沉积过程正常，此类区域仍保留Hop1蛋白，并可在粗线期（pachynema）持续发生DSB形成。Hop1的差异保留依赖于解组装酶Pch2/TRIP13：该酶优先从远离端粒的序列中移除Hop1，其活性受组蛋白去乙酰化酶Sir2与核孔蛋白Nup2的调控。
值得注意的是，各染色体上EARs的大小均一，这使得粗线期短染色体上的DSB与修复信号比例异常偏高，表明EARs在一定程度上解释了短染色体异常高的重组率。

资助编号：研究项目编号#6-FY16-208
项目名称：小染色体的减数分裂分离
资助方：美国出生缺陷基金会（March of Dimes Foundation）
所属机构：纽约大学（NEW YORK UNIVERSITY）
研究者姓名：安德烈亚斯·霍克瓦格纳（Andreas Hochwagen）

本研究针对减数分裂过程中酿酒酵母（Saccharomyces cerevisiae）内的Hop1、Red1、Zip1、pH2A、Mek1及Rad51靶标开展染色质免疫沉淀测序（chromatin immunoprecipitation sequencing, ChIP-seq）分析。每个bedgraph文件均为两份生物学重复样本的合并结果，每份生物学重复均包含配对的Input对照样本与ChIP实验样本。

请注意，由于处理后数据由多份样本联合生成，各样本的描述字段中已标注对应的处理后数据文件。