酿酒酵母染色体末端减数分裂轴蛋白沉积与DNA双链断裂诱导的可分离下调机制
Separable downmodulation of meiotic axis protein deposition and DNA break induction at chromosome ends
酿酒酵母染色体末端20 kb内重组促进轴蛋白富集偏低与DNA双链断裂（DSB）下调，由多种常具染色体特异性的抑制机制共同造成。轴蛋白抑制依赖组蛋白甲基转移酶Dot1和Sir沉默复合体，Dot1至少部分不依赖其经典靶点H3K79抑制Sir活性；Sir复合体则通过限制启动子开放度抑制少数隐蔽热点的DSB诱导。dot1和sir3突变体中末端DSB减少仍大部分存在，提示还有其他调控层参与。
来源：eLife · doi.org
In many organisms, meiotic crossover recombination is suppressed near the extreme ends of chromosomes. Here, we show that multiple, often chromosome-specific, suppressive mechanisms with differing ranges contribute to the consistently low enrichment of recombination-promoting axis proteins and the downregulation of DNA double-strand breaks (DSBs) within 20 kb of telomeres in Saccharomyces cerevisiae . Suppression of axis proteins is associated with cis -encoded signals and correlates with reduced coding density, although whether this sequence feature actively drives suppression remains to be determined. In addition, axis protein suppression requires the histone methyltransferase Dot1 and the Sir silencing complex. We show that Dot1 suppresses Sir complex activity at least in part independently of its canonical target, H3K79, to downmodulate axis protein deposition near chromosome ends. In parallel, the Sir complex, but not Dot1, suppresses the induction of DSBs at a small number of cryptic hotspots by limiting the openness of promoters, the preferred sites of meiotic DSB formation. Much of the reduced DSB induction near chromosome ends persists in dot1 and sir3 mutants, indicating that additional layers of regulation contribute to the robust reduction of meiotic recombination effectors near chromosome ends.