Zhang Tao, Paulson James R, Bakhrebah Muhammed, Kim Ji Hun, Nowell Cameron, Kalitsis Paul, Hudson Damien F
Murdoch Childrens Research Institute, Royal Children's Hospital, Melbourne, VIC, 3052, Australia.
Department of Paediatrics, University of Melbourne, Royal Children's Hospital, Melbourne, VIC, 3052, Australia.
Chromosome Res. 2016 May;24(2):243-69. doi: 10.1007/s10577-016-9519-7. Epub 2016 Mar 23.
Condensin is an integral component of the mitotic chromosome condensation machinery, which ensures orderly segregation of chromosomes during cell division. In metazoans, condensin exists as two complexes, condensin I and II. It is not yet clear what roles these complexes may play outside mitosis, and so we have examined their behaviour both in normal interphase and in premature chromosome condensation (PCC). We find that a small fraction of condensin I is retained in interphase nuclei, and our data suggests that this interphase nuclear condensin I is active in both gene regulation and chromosome condensation. Furthermore, live cell imaging demonstrates condensin II dramatically increases on G1 nuclei following completion of mitosis. Our PCC studies show condensins I and II and topoisomerase II localise to the chromosome axis in G1-PCC and G2/M-PCC, while KIF4 binding is altered. Individually, condensins I and II are dispensable for PCC. However, when both are knocked out, G1-PCC chromatids are less well structured. Our results define new roles for the condensins during interphase and provide new information about the mechanism of PCC.
凝缩蛋白是有丝分裂染色体凝聚机制的一个不可或缺的组成部分,它确保细胞分裂过程中染色体的有序分离。在后生动物中,凝缩蛋白以两种复合物的形式存在,即凝缩蛋白I和凝缩蛋白II。目前尚不清楚这些复合物在有丝分裂之外可能发挥什么作用,因此我们研究了它们在正常间期和早熟染色体凝聚(PCC)中的行为。我们发现一小部分凝缩蛋白I保留在间期细胞核中,我们的数据表明这种间期核凝缩蛋白I在基因调控和染色体凝聚中均有活性。此外,活细胞成像显示,有丝分裂完成后,凝缩蛋白II在G1期细胞核上显著增加。我们的PCC研究表明,凝缩蛋白I和II以及拓扑异构酶II在G1-PCC和G2/M-PCC中定位于染色体轴,而KIF4的结合发生了改变。单独来看,凝缩蛋白I和II对于PCC来说并非必需。然而,当两者都被敲除时,G1-PCC染色单体的结构就不那么好了。我们的结果确定了凝缩蛋白在间期的新作用,并提供了有关PCC机制的新信息。