Sonneville Remi, Craig Gillian, Labib Karim, Gartner Anton, Blow J Julian
Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK; MRC Protein Phosphorylation and Ubiquitylation Unit, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
Cell Rep. 2015 Jul 21;12(3):405-17. doi: 10.1016/j.celrep.2015.06.046. Epub 2015 Jul 9.
During cell division, chromatin alternates between a condensed state to facilitate chromosome segregation and a decondensed form when DNA replicates. In most tissues, S phase and mitosis are separated by defined G1 and G2 gap phases, but early embryogenesis involves rapid oscillations between replication and mitosis. Using Caenorhabditis elegans embryos as a model system, we show that chromosome condensation and condensin II concentration on chromosomal axes require replicated DNA. In addition, we found that, during late telophase, replication initiates on condensed chromosomes and promotes the rapid decondensation of the chromatin. Upon replication initiation, the CDC-45-MCM-GINS (CMG) DNA helicase drives the release of condensin I complexes from chromatin and the activation or displacement of inactive MCM-2-7 complexes, which together with the nucleoporin MEL-28/ELYS tethers condensed chromatin to the nuclear envelope, thereby promoting chromatin decondensation. Our results show how, in an early embryo, the chromosome-condensation cycle is functionally linked with DNA replication.
在细胞分裂过程中,染色质在浓缩状态(以促进染色体分离)和DNA复制时的解浓缩状态之间交替。在大多数组织中,S期和有丝分裂由明确的G1期和G2期间隔分开,但早期胚胎发育涉及复制和有丝分裂之间的快速振荡。利用秀丽隐杆线虫胚胎作为模型系统,我们发现染色体浓缩和凝聚素II在染色体轴上的富集需要已复制的DNA。此外,我们发现,在末期后期,复制在浓缩染色体上起始,并促进染色质的快速解浓缩。复制起始时,CDC-45-MCM-GINS(CMG)DNA解旋酶驱动凝聚素I复合物从染色质上释放,并激活或取代无活性的MCM-2-7复合物;MCM-2-7复合物与核孔蛋白MEL-28/ELYS一起将浓缩染色质连接到核膜上,从而促进染色质解浓缩。我们的结果表明,在早期胚胎中,染色体浓缩循环如何在功能上与DNA复制相联系。