Department of Cellular and Molecular Medicine, Arizona Cancer Center, University of Arizona, Tucson, AZ 85721, USA.
J Cell Biol. 2013 Apr 1;201(1):49-63. doi: 10.1083/jcb.201207183. Epub 2013 Mar 25.
Condensin complexes play vital roles in chromosome condensation during mitosis and meiosis. Condensin II uniquely localizes to chromatin throughout the cell cycle and, in addition to its mitotic duties, modulates chromosome organization and gene expression during interphase. Mitotic condensin activity is regulated by phosphorylation, but mechanisms that regulate condensin II during interphase are unclear. Here, we report that condensin II is inactivated when its subunit Cap-H2 is targeted for degradation by the SCF(Slimb) ubiquitin ligase complex and that disruption of this process dramatically changed interphase chromatin organization. Inhibition of SCF(Slimb) function reorganized interphase chromosomes into dense, compact domains and disrupted homologue pairing in both cultured Drosophila cells and in vivo, but these effects were rescued by condensin II inactivation. Furthermore, Cap-H2 stabilization distorted nuclear envelopes and dispersed Cid/CENP-A on interphase chromosomes. Therefore, SCF(Slimb)-mediated down-regulation of condensin II is required to maintain proper organization and morphology of the interphase nucleus.
凝聚素复合物在有丝分裂和减数分裂过程中染色体凝聚中发挥着至关重要的作用。凝聚素 II 在整个细胞周期中独特地定位于染色质上，除了有丝分裂的职责外，还在有丝分裂间期调节染色体组织和基因表达。有丝分裂凝聚素的活性受磷酸化调节，但调节有丝分裂间期凝聚素 II 的机制尚不清楚。在这里，我们报告说，当其亚基 Cap-H2 被 SCF(Slimb)泛素连接酶复合物靶向降解时，凝聚素 II 失活，并且破坏这一过程会显著改变有丝分裂间期染色质的组织。抑制 SCF(Slimb)的功能会将有丝分裂间期染色体重新组织成密集、紧凑的域，并破坏培养的果蝇细胞和体内同源物配对，但这些影响可以通过凝聚素 II 的失活来挽救。此外，Cap-H2 的稳定会扭曲核膜，并在有丝分裂间期染色体上分散 Cid/CENP-A。因此，需要 SCF(Slimb)介导的凝聚素 II 的下调来维持有丝分裂间期核的适当组织和形态。
