Fred Hutchinson Cancer Research Center, Division of Basic Sciences, Seattle, WA 98109, USA.
Cell. 2010 Jul 23;142(2):243-55. doi: 10.1016/j.cell.2010.05.041.
Crossovers between meiotic homologs are crucial for their proper segregation, and crossover number and position are carefully controlled. Crossover homeostasis in budding yeast maintains crossovers at the expense of noncrossovers when double-strand DNA break (DSB) frequency is reduced. The mechanism of maintaining constant crossover levels in other species has been unknown. Here we investigate in fission yeast a different aspect of crossover control--the near invariance of crossover frequency per kb of DNA despite large variations in DSB intensity across the genome. Crossover invariance involves the choice of sister chromatid versus homolog for DSB repair. At strong DSB hotspots, intersister repair outnumbers interhomolog repair approximately 3:1, but our genetic and physical data indicate the converse in DSB-cold regions. This unanticipated mechanism of crossover control may operate in many species and explain, for example, the large excess of DSBs over crossovers and the repair of DSBs on unpaired chromosomes in diverse species.
减数分裂同源体之间的交叉对于它们的正确分离至关重要,并且交叉的数量和位置受到严格控制。在芽殖酵母中,当双链 DNA 断裂 (DSB) 频率降低时,交叉同源体的平衡会以非交叉同源体为代价来维持交叉。其他物种中维持恒定交叉水平的机制尚不清楚。在这里,我们在裂殖酵母中研究了交叉控制的另一个方面——尽管基因组中 DSB 强度存在很大差异,但每个 kb DNA 的交叉频率几乎保持不变。交叉不变性涉及到姐妹染色单体与同源体之间的 DSB 修复选择。在强 DSB 热点处,姐妹间修复的数量大约是同源间修复的 3:1,但我们的遗传和物理数据表明在 DSB 冷区则相反。这种出乎意料的交叉控制机制可能在许多物种中起作用,并解释了例如,DSB 数量远远超过交叉,以及在不同物种中未配对染色体上的 DSB 修复等现象。