Centro Andaluz de Biologia del Desarrollo, Universidad Pablo de Olavide, Seville 41013, Spain.
Department of Microbiology and Immunology, Columbia University College of Physicians and Surgeons, New York, NY 10032.
Mol Biol Cell. 2019 Oct 1;30(21):2695-2708. doi: 10.1091/mbc.E19-05-0301. Epub 2019 Sep 4.
Although the function of microtubules (MTs) in chromosomal segregation during mitosis is well characterized, much less is known about the role of MTs in chromosomal functions during interphase. In the fission yeast , dynamic cytoplasmic MT bundles move chromosomes in an oscillatory manner during interphase via linkages through the nuclear envelope (NE) at the spindle pole body (SPB) and other sites. Mto1 is a cytoplasmic factor that mediates the nucleation and attachment of cytoplasmic MTs to the nucleus. Here, we test the function of these cytoplasmic MTs and Mto1 on DNA repair and recombination during interphase. We find that cells exhibit defects in DNA repair and homologous recombination (HR) and abnormal DNA repair factory dynamics. In these cells, sister chromatids are not properly paired, and binding of Rad21 cohesin subunit along chromosomal arms is reduced. Our findings suggest a model in which cytoplasmic MTs and Mto1 facilitate efficient DNA repair and HR by promoting dynamic chromosomal organization and cohesion in the nucleus.
尽管微管(MTs)在有丝分裂过程中的染色体分离中的功能已经得到很好的描述,但 MTs 在间期染色体功能中的作用知之甚少。在裂殖酵母中,动态细胞质 MT 束通过与纺锤体极体(SPB)和其他部位的核膜(NE)的连接,以振荡方式在间期移动染色体。Mto1 是一种细胞质因子,介导细胞质 MT 到核的成核和附着。在这里,我们测试了这些细胞质 MT 和 Mto1 在间期 DNA 修复和重组中的功能。我们发现,细胞在 DNA 修复和同源重组(HR)以及异常 DNA 修复工厂动力学方面存在缺陷。在这些细胞中,姐妹染色单体没有正确配对,并且沿着染色体臂的 Rad21 黏合蛋白亚基的结合减少。我们的研究结果表明,细胞质 MT 和 Mto1 通过促进细胞核中动态染色体组织和黏合,促进有效的 DNA 修复和 HR。