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Chromosome Bridges Maintain Kinetochore-Microtubule Attachment throughout Mitosis and Rarely Break during Anaphase

机译:染色体桥在整个有丝分裂期间都保持着线粒体-微管的附着,并且在后期很少断裂

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摘要

Accurate chromosome segregation during cell division is essential to maintain genome stability, and chromosome segregation errors are causally linked to genetic disorders and cancer. An anaphase chromosome bridge is a particular chromosome segregation error observed in cells that enter mitosis with fused chromosomes/sister chromatids. The widely accepted Breakage/Fusion/Bridge cycle model proposes that anaphase chromosome bridges break during mitosis to generate chromosome ends that will fuse during the following cell cycle, thus forming new bridges that will break, and so on. However, various studies have also shown a link between chromosome bridges and aneuploidy and/or polyploidy. In this study, we investigated the behavior and properties of chromosome bridges during mitosis, with the idea to gain insight into the potential mechanism underlying chromosome bridge-induced aneuploidy. We find that only a small number of chromosome bridges break during anaphase, whereas the rest persist through mitosis into the subsequent cell cycle. We also find that the microtubule bundles (k-fibers) bound to bridge kinetochores are not prone to breakage/detachment, thus supporting the conclusion that k-fiber detachment is not the cause of chromosome bridge-induced aneuploidy. Instead, our data suggest that while the microtubules bound to the kinetochores of normally segregating chromosomes shorten substantially during anaphase, the k-fibers bound to bridge kinetochores shorten only slightly, and may even lengthen, during anaphase. This causes some of the bridge kinetochores/chromosomes to lag behind in a position that is proximal to the cell/spindle equator and may cause the bridged chromosomes to be segregated into the same daughter nucleus or to form a micronucleus.
机译:细胞分裂过程中准确的染色体分离对于维持基因组稳定性至关重要,而染色体分离错误与遗传疾病和癌症有因果关系。后期染色体桥是在融合染色体/姐妹染色单体进入有丝分裂的细胞中观察到的特定染色体分离错误。广泛接受的“断裂/融合/桥循环”模型建议,有后期染色体桥在有丝分裂过程中断裂,产生染色体末端,该末端将在随后的细胞周期中融合,从而形成新的桥,然后断裂,依此类推。但是,各种研究也表明染色体桥与非整倍性和/或多倍性之间存在联系。在这项研究中,我们调查了有丝分裂期间染色体桥的行为和性质,以期深入了解染色体桥诱导的非整倍性的潜在机制。我们发现后期只有少数染色体桥断裂,而其余的则通过有丝分裂持续进入随后的细胞周期。我们还发现绑定到桥动子的微管束(k纤维)不易于断裂/分离,因此支持了k纤维分离不是染色体桥诱导的非整倍性的原因的结论。取而代之的是,我们的数据表明,与正常分离染色体的动植物结合的微管在后期显着缩短,而与桥动植物结合的k纤维在后期却仅略微缩短,甚至可能加长。这会导致某些桥动子体/染色体在靠近细胞/主轴赤道的位置滞后,并可能导致桥连的染色体被分离到相同的子核或形成微核。

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