Institute for Research in Immunology and Cancer, Université de Montréal, Montreal, Canada.
Département de biochimie et médecine moléculaire, Université de Montréal, Montreal, Canada.
PLoS Biol. 2024 Aug 26;22(8):e3002780. doi: 10.1371/journal.pbio.3002780. eCollection 2024 Aug.
In animals, mitosis involves the breakdown of the nuclear envelope and the sorting of individualized, condensed chromosomes. During mitotic exit, emerging nuclei reassemble a nuclear envelope around a single mass of interconnecting chromosomes. The molecular mechanisms of nuclear reassembly are incompletely understood. Moreover, the cellular and physiological consequences of defects in this process are largely unexplored. Here, we have characterized a mechanism essential for nuclear reassembly in Drosophila. We show that Ankle2 promotes the PP2A-dependent recruitment of BAF and Lamin at reassembling nuclei, and that failures in this mechanism result in severe nuclear defects after mitosis. We then took advantage of perturbations in this mechanism to investigate the physiological responses to nuclear reassembly defects during tissue development in vivo. Partial depletion of Ankle2, BAF, or Lamin in imaginal wing discs results in wing development defects accompanied by apoptosis. We found that blocking apoptosis strongly enhances developmental defects. Blocking p53 does not prevent apoptosis but enhances defects due to the loss of a cell cycle checkpoint. Our results suggest that apoptotic and p53-dependent responses play a crucial role in safeguarding tissue development in response to sporadic nuclear reassembly defects.
在动物中，有丝分裂涉及核膜的分解和个体化、浓缩染色体的分类。在有丝分裂退出期间，新出现的核重新围绕单个连接的染色体团组装核膜。核重装配的分子机制尚未完全理解。此外，该过程缺陷的细胞和生理后果在很大程度上仍未得到探索。在这里，我们描述了果蝇中核重装配所必需的一种机制。我们表明，Ankle2 促进了 PP2A 依赖性 BAF 和 Lamin 在重新组装核中的募集，并且该机制的故障会导致有丝分裂后严重的核缺陷。然后，我们利用该机制的干扰来研究体内组织发育过程中核重装配缺陷的生理反应。在 imaginal 翅片中部分耗尽 Ankle2、BAF 或 Lamin 会导致翅膀发育缺陷并伴有细胞凋亡。我们发现，阻断细胞凋亡会强烈增强发育缺陷。阻断 p53 不会阻止凋亡，但会增强由于细胞周期检查点丧失而导致的缺陷。我们的结果表明，凋亡和 p53 依赖性反应在保护组织发育方面起着至关重要的作用，以应对偶发性核重装配缺陷。
