Department of Pathology, Kimmel Center for Biology and Medicine at the Skirball Institute, New York University School of Medicine, New York, New York 10016, USA.
Centre for Chromosome Biology, School of Natural Sciences, National University of Ireland Galway, Ireland.
Genes Dev. 2019 Mar 1;33(5-6):276-281. doi: 10.1101/gad.321836.118. Epub 2019 Feb 25.
Formation of individualized sister chromatids is essential for their accurate segregation. In budding yeast, while most of the genome segregates at the metaphase to anaphase transition, resolution of the ribosomal DNA (rDNA) repeats is delayed. The timing and mechanism in human cells is unknown. Here we show that resolution of human rDNA occurs in anaphase after the bulk of the genome, dependent on tankyrase 1, condensin II, and topoisomerase IIα. Defective resolution leads to rDNA bridges, rDNA damage, and aneuploidy of an rDNA-containing acrocentric chromosome. Thus, temporal regulation of rDNA segregation is conserved between yeast and man and is essential for genome integrity.
姐妹染色单体的个体化形成对于它们的准确分离至关重要。在芽殖酵母中,尽管大部分基因组在有丝分裂中期到后期过渡时分离,但核糖体 DNA(rDNA) 重复序列的分离却被延迟。在人类细胞中,其时间和机制尚不清楚。在这里,我们表明人类 rDNA 的分离发生在后期,晚于大部分基因组,这依赖于 Tankyrase1、凝聚素 II 和拓扑异构酶 IIα。分辨率的缺陷会导致 rDNA 桥、rDNA 损伤以及含有 rDNA 的近端着丝粒染色体的非整倍体。因此,rDNA 分离的时间调控在酵母和人类之间是保守的,对于基因组完整性是必不可少的。