Programme Equipe Labéllisée Ligue Contre le Cancer - Team Cell Cycle & Development - Université de Paris, CNRS, Institut Jacques Monod, Paris, France.
Department of Chromosome Biology, Max Perutz Laboratories, University of Vienna, Vienna Biocenter, Vienna, Austria.
Elife. 2020 Oct 8;9:e59510. doi: 10.7554/eLife.59510.
Life of sexually reproducing organisms starts with the fusion of the haploid egg and sperm gametes to form the genome of a new diploid organism. Using the newly fertilized zygote, we show that the mitotic Polo-like kinase PLK-1 phosphorylates the lamin LMN-1 to promote timely lamina disassembly and subsequent merging of the parental genomes into a single nucleus after mitosis. Expression of non-phosphorylatable versions of LMN-1, which affect lamina depolymerization during mitosis, is sufficient to prevent the mixing of the parental chromosomes into a single nucleus in daughter cells. Finally, we recapitulate lamina depolymerization by PLK-1 in vitro demonstrating that LMN-1 is a direct PLK-1 target. Our findings indicate that the timely removal of lamin is essential for the merging of parental chromosomes at the beginning of life in and possibly also in humans, where a defect in this process might be fatal for embryo development.
有性繁殖生物的生命始于单倍体卵子和精子配子的融合，形成新的二倍体生物的基因组。利用新受精的合子，我们表明有丝分裂中的 Polo 样激酶 PLK-1 磷酸化核纤层蛋白 LMN-1，以促进有丝分裂后核纤层的及时解体和随后的亲本基因组融合到单个核中。表达非磷酸化的 LMN-1 版本，其影响有丝分裂期间核纤层的解聚，足以防止亲本染色体在子细胞中混合到单个核中。最后，我们在体外重新构建了 PLK-1 介导的核纤层解聚，证明 LMN-1 是 PLK-1 的直接靶标。我们的发现表明，核纤层的及时去除对于生命开始时亲本染色体的融合是至关重要的，这可能在人类中也是如此，在这个过程中，如果出现缺陷，可能对胚胎发育是致命的。
