Smith K N, Penkner A, Ohta K, Klein F, Nicolas A
Institut Curie, Section de Recherche, CNRS-UMR144 Cedex 05 75248, Paris, France.
Curr Biol. 2001 Jan 23;11(2):88-97. doi: 10.1016/s0960-9822(01)00026-4.
The life cycle of most eukaryotic organisms includes a meiotic phase, in which diploid parental cells produce haploid gametes. During meiosis a single round of DNA replication is followed by two rounds of chromosome segregation. In the first, or reductional, division (meiosis I), which is unique to meiotic cells, homologous chromosomes segregate from one another, whereas in the second, or equational, division (Meiosis II) sister centromeres disjoin. Meiotic DNA replication precedes the initiation of recombination by programmed Spo11-dependent DNA double-strand breaks. Recent reports that meiosis-specific cohesion is established during meiotic S phase and that the length of S phase is modified by recombination factors (Spo11 and Rec8) raise the possibility that replication plays a fundamental role in the recombination process.
To address how replication influences the initiation of recombination, we have used mutations in the B-type cyclin genes CLB5 and CLB6, which specifically prevent premeiotic replication in the yeast Saccharomyces cerevisiae. We find that clb5 and clb5 clb6 but not clb6 mutants are defective in DSB induction and prior associated changes in chromatin accessibility, heteroallelic recombination, and SC formation. The severity of these phenotypes in each mutant reflects the extent of replication impairment.
This assemblage of phenotypes reveals roles for CLB5 and CLB6 not only in DNA replication but also in other key events of meiotic prophase. Links between the function of CLB5 and CLB6 in activating meiotic DNA replication and their effects on subsequent events are discussed.
大多数真核生物的生命周期包括减数分裂阶段，在此阶段二倍体亲代细胞产生单倍体配子。在减数分裂过程中，一轮DNA复制之后是两轮染色体分离。在第一次即减数分裂（减数分裂I）中，这是减数分裂细胞特有的，同源染色体彼此分离，而在第二次即均等分裂（减数分裂II）中，姐妹着丝粒分离。减数分裂DNA复制先于由程序性的Spo11依赖性DNA双链断裂引发的重组。最近有报道称，减数分裂特异性黏连在减数分裂S期建立，并且S期的长度由重组因子（Spo11和Rec8）调节，这增加了复制在重组过程中起基本作用的可能性。
为了研究复制如何影响重组的起始，我们利用了B型细胞周期蛋白基因CLB5和CLB6中的突变，这些突变特异性地阻止酿酒酵母中的减数分裂前复制。我们发现，clb5和clb5 clb6突变体，但不是clb6突变体，在DSB诱导以及染色质可及性、杂合等位基因重组和SC形成的先前相关变化方面存在缺陷。每个突变体中这些表型的严重程度反映了复制受损的程度。
这些表型组合揭示了CLB5和CLB6不仅在DNA复制中，而且在减数分裂前期的其他关键事件中所起的作用。讨论了CLB5和CLB6在激活减数分裂DNA复制中的功能与其对后续事件的影响之间的联系。
