Mitotic chromosome alignment ensures mitotic fidelity by promoting interchromosomal compaction during anaphase
Mitotic chromosome alignment ensures mitotic fidelity by promoting interchromosomal compaction during anaphase
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DOI：
10.1083/jcb.201807228
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发表时间：
2019-04-01
影响因子：
7.8
通讯作者：
Stumpff, Jason
中科院分区：
文献类型：
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作者：
Fonseca, Cindy L.;Malaby, Heidi L. H.;Stumpff, Jason
有丝分裂纺锤体赤道处的染色体排列是细胞分裂过程中高度保守的步骤;然而，其对基因组稳定性和细胞适应性的重要性尚不清楚。缺乏KIF 18 A的正常哺乳动物体细胞在没有对齐染色体的情况下完成细胞分裂。这些缺失的细胞在体外和体内显示正常的染色体拷贝数，表明染色体排列在很大程度上是为了维持整倍性。然而，我们发现，染色体排列的损失导致染色体间压实缺陷在后期，染色体异常组织成一个单一的核在有丝分裂出口，并在体外和体内形成微核。这些缺陷减缓细胞增殖，并与小鼠出生后生长和存活受损有关。我们的研究支持一个模型，其中有丝分裂染色体的排列促进染色体正确组织成一个单一的细胞核，并通过确保染色体分离作为一个紧凑的质量在后期持续增殖。
Chromosome alignment at the equator of the mitotic spindle is a highly conserved step during cell division; however, its importance to genomic stability and cellular fitness is not understood. Normal mammalian somatic cells lacking KIF18A function complete cell division without aligning chromosomes. These alignment-deficient cells display normal chromosome copy numbers in vitro and in vivo, suggesting that chromosome alignment is largely dispensable for maintenance of euploidy. However, we find that loss of chromosome alignment leads to interchromosomal compaction defects during anaphase, abnormal organization of chromosomes into a single nucleus at mitotic exit, and the formation of micronuclei in vitro and in vivo. These defects slow cell proliferation and are associated with impaired postnatal growth and survival in mice. Our studies support a model in which the alignment of mitotic chromosomes promotes proper organization of chromosomes into a single nucleus and continued proliferation by ensuring that chromosomes segregate as a compact mass during anaphase.