Laboratory of Biochemistry and Molecular Biology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, United States of America.
PLoS Biol. 2010 Oct 19;8(10):e1000520. doi: 10.1371/journal.pbio.1000520.
Recombination between homologous chromosomes of different parental origin (homologs) is necessary for their accurate segregation during meiosis. It has been suggested that meiotic inter-homolog recombination is promoted by a barrier to inter-sister-chromatid recombination, imposed by meiosis-specific components of the chromosome axis. Consistent with this, measures of Holliday junction-containing recombination intermediates (joint molecules [JMs]) show a strong bias towards inter-homolog and against inter-sister JMs. However, recombination between sister chromatids also has an important role in meiosis. The genomes of diploid organisms in natural populations are highly polymorphic for insertions and deletions, and meiotic double-strand breaks (DSBs) that form within such polymorphic regions must be repaired by inter-sister recombination. Efforts to study inter-sister recombination during meiosis, in particular to determine recombination frequencies and mechanisms, have been constrained by the inability to monitor the products of inter-sister recombination. We present here molecular-level studies of inter-sister recombination during budding yeast meiosis. We examined events initiated by DSBs in regions that lack corresponding sequences on the homolog, and show that these DSBs are efficiently repaired by inter-sister recombination. This occurs with the same timing as inter-homolog recombination, but with reduced (2- to 3-fold) yields of JMs. Loss of the meiotic-chromosome-axis-associated kinase Mek1 accelerates inter-sister DSB repair and markedly increases inter-sister JM frequencies. Furthermore, inter-sister JMs formed in mek1Δ mutants are preferentially lost, while inter-homolog JMs are maintained. These findings indicate that inter-sister recombination occurs frequently during budding yeast meiosis, with the possibility that up to one-third of all recombination events occur between sister chromatids. We suggest that a Mek1-dependent reduction in the rate of inter-sister repair, combined with the destabilization of inter-sister JMs, promotes inter-homolog recombination while retaining the capacity for inter-sister recombination when inter-homolog recombination is not possible.
不同亲本来源（同源）的染色体之间的重组对于减数分裂中它们的准确分离是必要的。有人提出，减数分裂中姐妹染色单体之间的重组受到由染色体轴的减数分裂特异性成分施加的对姐妹染色单体之间重组的障碍的促进。与这一致的是，含有 Holliday 连接的重组中间体（连接分子[JMs]）的测量结果强烈偏向于同源之间，而不是姐妹之间的 JMs。然而，姐妹染色单体之间的重组在减数分裂中也具有重要作用。在自然种群中的二倍体生物的基因组中，插入和缺失高度多态性，并且在这种多态性区域内形成的减数分裂双链断裂（DSBs）必须通过姐妹染色单体之间的重组来修复。在减数分裂过程中研究姐妹染色单体之间的重组，特别是确定重组频率和机制的努力，受到无法监测姐妹染色单体之间重组产物的限制。我们在这里介绍了在芽殖酵母减数分裂过程中姐妹染色单体之间重组的分子水平研究。我们检查了在同源染色体上没有相应序列的区域中由 DSB 引发的事件，并表明这些 DSB 通过姐妹染色单体之间的重组有效地修复。这与同源之间的重组发生在相同的时间，但 JMs 的产量降低（2-3 倍）。减数分裂染色体轴相关激酶 Mek1 的缺失加速了姐妹染色单体 DSB 的修复，并显著增加了姐妹染色单体 JM 的频率。此外，在 mek1Δ突变体中形成的姐妹染色单体 JMs 优先丢失，而同源 JMs 则被维持。这些发现表明，姐妹染色单体之间的重组在芽殖酵母减数分裂中频繁发生，可能高达三分之一的所有重组事件发生在姐妹染色单体之间。我们认为，Mek1 依赖性的姐妹染色单体修复速率降低，加上姐妹染色单体 JMs 的不稳定性，促进了同源重组，同时在不可能发生同源重组时保留了姐妹染色单体重组的能力。
