Department of Molecular, Cell, and Developmental Biology, University of California, Santa Cruz, Santa Cruz, CA 95064, USA.
Cell. 2010 Jan 22;140(2):235-45. doi: 10.1016/j.cell.2009.12.043.
The mechanisms that safeguard cells against chromosomal instability (CIN) are of great interest, as CIN contributes to tumorigenesis. To gain insight into these mechanisms, we studied the behavior of cells entering mitosis with damaged chromosomes. We used the endonuclease I-CreI to generate acentric chromosomes in Drosophila larvae. While I-CreI expression produces acentric chromosomes in the majority of neuronal stem cells, remarkably, it has no effect on adult survival. Our live studies reveal that acentric chromatids segregate efficiently to opposite poles. The acentric chromatid poleward movement is mediated through DNA tethers decorated with BubR1, Polo, INCENP, and Aurora-B. Reduced BubR1 or Polo function results in abnormal segregation of acentric chromatids, a decrease in acentric chromosome tethering, and a great reduction in adult survival. We propose that BubR1 and Polo facilitate the accurate segregation of acentric chromatids by maintaining the integrity of the tethers that connect acentric chromosomes to their centric partners.
细胞对抗染色体不稳定性（CIN）的机制引起了人们的极大兴趣，因为 CIN 有助于肿瘤发生。为了深入了解这些机制，我们研究了带有受损染色体进入有丝分裂的细胞的行为。我们使用内切酶 I-CreI 在果蝇幼虫中产生无着丝粒染色体。虽然 I-CreI 的表达在大多数神经元干细胞中产生无着丝粒染色体，但令人惊讶的是，它对成虫的存活没有影响。我们的活体研究表明，无着丝粒染色单体有效地分离到相反的两极。无着丝粒染色单体的向极运动是通过带有 BubR1、Polo、INCENP 和 Aurora-B 的 DNA 系绳介导的。降低 BubR1 或 Polo 的功能会导致无着丝粒染色单体的异常分离、无着丝粒染色体系绳的减少以及成虫存活率的大幅降低。我们提出，BubR1 和 Polo 通过维持将无着丝粒染色体与其着丝粒伙伴连接起来的系绳的完整性，促进无着丝粒染色单体的准确分离。
