Abstract
SummaryDuring 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.
Highlights
Cell-cycle progression requires the ordered succession of cellcycle stages, and checkpoints ensure that critical cell-cycle events such as DNA replication or chromosome alignment are completed before subsequent stages can occur
Using Caenorhabditis elegans embryos as a model system, we show that chromosome condensation and condensin II concentration on chromosomal axes require replicated DNA
The CDC-45-MCMGINS (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 MEL28/ELYS tethers condensed chromatin to the nuclear envelope, thereby promoting chromatin decondensation
Summary
Cell-cycle progression requires the ordered succession of cellcycle stages, and checkpoints ensure that critical cell-cycle events such as DNA replication or chromosome alignment are completed before subsequent stages can occur. Changes in cyclin-dependent kinase (CDK) kinase activity and differential cyclin association drive major transitions such as the initiation of S phase, mitosis, and the subsequent segregation of chromatids. Faithful chromosome segregation requires the structural reorganization of chromosomes into condensed metaphase chromosomes, which is needed for the segregation of chromatids during anaphase. Chromosome decondensation facilitates transcription and DNA replication. S phase and mitosis alternate without apparent G1 or G2 phases. Decondensation, DNA replication, and re-condensation occur in a short period and could potentially overlap. We know little about how DNA replication and chromatin condensation and decondensation are coordinated
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