Institut Jean-Pierre Bourgin, UMR1318 INRA-AgroParisTech, Université Paris-Saclay, 78000 Versailles, France.
Department of Plant Biotechnology and Bioinformatics, Ghent University, B-9052 Ghent, Belgium.
Proc Natl Acad Sci U S A. 2019 Aug 6;116(32):16018-16027. doi: 10.1073/pnas.1906237116. Epub 2019 Jul 19.
Chromosome distribution at anaphase of mitosis and meiosis is triggered by separase, an evolutionarily conserved protease. Separase must be tightly regulated to prevent the untimely release of chromatid cohesion and disastrous chromosome distribution defects. Securin is the key inhibitor of separase in animals and fungi, but has not been identified in other eukaryotic lineages. Here, we identified PATRONUS1 and PATRONUS2 (PANS1 and PANS2) as the homologs of securin. Disruption of is known to lead to the premature separation of chromosomes at meiosis, and the simultaneous disruption of and is lethal. Here, we show that PANS1 targeting by the anaphase-promoting complex is required to trigger chromosome separation, mirroring the regulation of securin. We showed that PANS1 acts independently from Shugosins. In a genetic screen for suppressors, we identified mutants, showing that PANS1 and SEPARASE have antagonistic functions in vivo. Finally, we showed that the PANS1 and PANS2 proteins interact directly with SEPARASE. Altogether, our results show that PANS1 and PANS2 act as a plant securin. Remote sequence similarity was identified between the plant patronus family and animal securins, suggesting that they indeed derive from a common ancestor. Identification of patronus as the elusive plant securin illustrates the extreme sequence divergence of this central regulator of mitosis and meiosis.
有丝分裂和减数分裂后期染色体的分离是由分离酶触发的,这是一种进化上保守的蛋白酶。为了防止染色单体的凝聚过早释放和灾难性的染色体分离缺陷,分离酶必须受到严格的调控。在动物和真菌中,securin 是分离酶的关键抑制剂,但在其他真核生物谱系中尚未被识别。在这里,我们鉴定了 PATRONUS1 和 PATRONUS2(PANS1 和 PANS2)为 securin 的同源物。已知 的破坏会导致减数分裂过程中染色体的过早分离,而 和 的同时破坏是致命的。在这里,我们表明,泛素连接酶复合物(APC)对 PANS1 的靶向作用是触发染色体分离所必需的,这与 securin 的调控相呼应。我们表明 PANS1 独立于 Shugosins 发挥作用。在针对 的遗传筛选中,我们鉴定了 突变体,表明 PANS1 和 SEPARASE 在体内具有拮抗作用。最后,我们表明 PANS1 和 PANS2 蛋白与 SEPARASE 直接相互作用。总之,我们的研究结果表明,PANS1 和 PANS2 作为植物 securin 发挥作用。植物 patronus 家族与动物 securins 之间存在远程序列相似性,这表明它们确实来自共同的祖先。鉴定 patronus 为难以捉摸的植物 securin 说明了这种有丝分裂和减数分裂的核心调节剂的极端序列分歧。