Department of Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, Hongo, Tokyo, Japan.
PLoS One. 2012;7(1):e30622. doi: 10.1371/journal.pone.0030622. Epub 2012 Jan 23.
The SCF (Skp1-Cul1-F-box) complex contributes to a variety of cellular events including meiotic cell cycle control, but its function during meiosis is not understood well. Here we describe a novel function of SCF/Skp1 in meiotic recombination and subsequent chromosome segregation. The skp1 temperature-sensitive mutant exhibited abnormal distribution of spindle microtubules in meiosis II, which turned out to originate from abnormal bending of the spindle in meiosis I. Bent spindles were reported in mitosis of this mutant, but it remained unknown how SCF could affect spindle morphology. We found that the meiotic bent spindle in skp1 cells was due to a hypertension generated by chromosome entanglement. The spindle bending was suppressed by inhibiting double strand break (DSB) formation, indicating that the entanglement was generated by the meiotic recombination machinery. Consistently, Rhp51/Rad51-Rad22/Rad52 foci persisted until meiosis I in skp1 cells, proving accumulation of recombination intermediates. Intriguingly bent spindles were also observed in the mutant of Fbh1, an F-box protein containing the DNA helicase domain, which is involved in meiotic recombination. Genetic evidence suggested its cooperation with SCF/Skp1. Thus, SCF/Skp1 together with Fbh1 is likely to function in the resolution of meiotic recombination intermediates, thereby ensuring proper chromosome segregation.
SCF（Skp1-Cul1-F-box）复合物参与多种细胞事件，包括减数分裂细胞周期控制，但它在减数分裂中的功能尚不清楚。在这里，我们描述了 SCF/Skp1 在减数分裂重组和随后的染色体分离中的一个新功能。skp1 温度敏感突变体在减数分裂 II 中表现出纺锤体微管的异常分布，这源于减数分裂 I 中纺锤体的异常弯曲。在该突变体的有丝分裂中曾报道过弯曲的纺锤体，但尚不清楚 SCF 如何影响纺锤体形态。我们发现 skp1 细胞中的减数分裂弯曲纺锤体是由于染色体缠绕产生的高血压。通过抑制双链断裂（DSB）形成抑制了纺锤体弯曲，表明这种缠绕是由减数分裂重组机制产生的。一致地，Rhp51/Rad51-Rad22/Rad52 焦点在 skp1 细胞中一直持续到减数分裂 I，证明了重组中间体的积累。有趣的是，在 Fbh1 突变体中也观察到了弯曲的纺锤体，Fbh1 是一种含有 DNA 解旋酶结构域的 F-box 蛋白，参与减数分裂重组。遗传证据表明它与 SCF/Skp1 合作。因此，SCF/Skp1 与 Fbh1 可能共同作用于减数分裂重组中间体的解决，从而确保正确的染色体分离。
