Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain.
Semin Cell Dev Biol. 2022 Mar;123:124-130. doi: 10.1016/j.semcdb.2021.03.004. Epub 2021 Mar 21.
The nuclear envelope surrounds the eukaryotic genome and, through the nuclear pore complexes, regulates transport in and out of the nucleus. Correct nucleo-cytoplasm compartmentations are essential for nuclear functions such as DNA replication or repair. During metazoan mitosis, the nuclear envelope disintegrates to allow the segregation of the two copies of DNA between daughter cells. At the end of mitosis, it reforms on each group of chromosomes in the daughter cells. However, nuclear envelope reformation is delayed on lagging chromosomes and DNA bridges. Defects in the coordination between nuclear envelope reformation and chromosome segregation impair the nuclear functions. Mechanical stress to which micronuclei and DNA bridges are subjected to combined with their particular architecture and the altered nuclear functions result in DNA damage. While micronuclei and DNA bridges were considered for more than 100 years as mere indicators of chromosomal instability, rapid technological advances are helping to better understand the biological consequences of these aberrant nuclear morphologies. Recent studies provide interesting evidence that micronuclei and chromatin bridges act as a key platforms for a catastrophic mutational process observed in cancers called chromothripsis and a trigger for the innate immune response. Therefore, they could affect cellular functions by both genetic and non-genetic means.
核膜围绕着真核生物的基因组，并通过核孔复合体调节核内外物质的运输。正确的核质区室分隔对于核功能（如 DNA 复制或修复）至关重要。在有丝分裂过程中，核膜解体，使 DNA 的两份拷贝在子细胞之间分离。在有丝分裂末期，它在子细胞的每组染色体上重新形成。然而，在滞后染色体和 DNA 桥处，核膜的重新形成会延迟。核膜形成与染色体分离之间协调的缺陷会损害核功能。微核和 DNA 桥所承受的机械压力，再加上它们特殊的结构和改变的核功能，导致 DNA 损伤。虽然微核和 DNA 桥作为染色体不稳定性的指标已经被研究了 100 多年，但快速的技术进步正在帮助更好地理解这些异常核形态的生物学后果。最近的研究提供了有趣的证据，表明微核和染色质桥作为一种称为染色体重排的灾难性突变过程的关键平台，以及先天免疫反应的触发因素。因此，它们可以通过遗传和非遗传方式影响细胞功能。
