Rattani Ahmed, Wolna Magda, Ploquin Mickael, Helmhart Wolfgang, Morrone Seamus, Mayer Bernd, Godwin Jonathan, Xu Wenqing, Stemmann Olaf, Pendas Alberto, Nasmyth Kim
Department of Biochemistry, University of Oxford, Oxford, United Kingdom.
Elife. 2013 Nov 5;2:e01133. doi: 10.7554/eLife.01133.
Accurate chromosome segregation depends on coordination between cohesion resolution and kinetochore-microtubule interactions (K-fibers), a process regulated by the spindle assembly checkpoint (SAC). How these diverse processes are coordinated remains unclear. We show that in mammalian oocytes Shugoshin-like protein 2 (Sgol2) in addition to protecting cohesin, plays an important role in turning off the SAC, in promoting the congression and bi-orientation of bivalents on meiosis I spindles, in facilitating formation of K-fibers and in limiting bivalent stretching. Sgol2's ability to protect cohesin depends on its interaction with PP2A, as is its ability to silence the SAC, with the latter being mediated by direct binding to Mad2. In contrast, its effect on bivalent stretching and K-fiber formation is independent of PP2A and mediated by recruitment of MCAK and inhibition of Aurora C kinase activity respectively. By virtue of its multiple interactions, Sgol2 links many of the processes essential for faithful chromosome segregation. DOI: http://dx.doi.org/10.7554/eLife.01133.001.
精确的染色体分离依赖于黏连蛋白解离与动粒-微管相互作用(动粒微管)之间的协调,这一过程由纺锤体组装检验点(SAC)调控。这些不同的过程是如何协调的仍不清楚。我们发现,在哺乳动物卵母细胞中,类守护蛋白2(Sgol2)除了保护黏连蛋白外,在关闭SAC、促进二价体在减数分裂I纺锤体上的汇聚和双定向、促进动粒微管的形成以及限制二价体拉伸方面发挥着重要作用。Sgol2保护黏连蛋白的能力取决于其与蛋白磷酸酶2A(PP2A)的相互作用,其使SAC沉默的能力也是如此,后者是通过直接结合Mad2介导的。相比之下,其对二价体拉伸和动粒微管形成的影响独立于PP2A,分别由招募微管运动蛋白XKCM1(MCAK)和抑制极光激酶C(Aurora C)活性介导。凭借其多种相互作用,Sgol2将许多对忠实染色体分离至关重要的过程联系起来。DOI: http://dx.doi.org/10.7554/eLife.01133.001