Department of Molecular Physiology and Biophysics, University of Vermont, Burlington, VT.
The Jackson Laboratory, Bar Harbor, ME.
J Cell Biol. 2019 Apr 1;218(4):1148-1163. doi: 10.1083/jcb.201807228. Epub 2019 Feb 7.
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.
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。正常的哺乳动物体细胞缺乏 KIF18A 功能仍能完成染色体排列，而不会完成细胞分裂。这些缺乏染色体排列的细胞在体外和体内显示出正常的染色体拷贝数，这表明染色体排列对于维持整倍体性在很大程度上是可有可无的。然而，我们发现染色体排列的缺失会导致后期染色体间的压缩缺陷、有丝分裂后期染色体异常地组织成单个核、以及体外和体内微核的形成。这些缺陷会减缓细胞增殖，并与小鼠出生后生长和存活受损有关。我们的研究支持这样一种模型，即有丝分裂染色体的排列通过确保染色体在后期作为一个紧凑的整体进行分离，从而促进染色体正确地组织成一个核，并继续增殖。
