Myung Kyungjae, Smith Stephanie, Kolodner Richard D
National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Proc Natl Acad Sci U S A. 2004 Nov 9;101(45):15980-5. doi: 10.1073/pnas.0407010101. Epub 2004 Oct 28.
The accumulation of gross chromosomal rearrangements (GCRs) is characteristic of cancer cells. Multiple pathways that prevent GCRs, including S-phase cell cycle checkpoints, homologous recombination, telomere maintenance, suppression of de novo telomere addition, chromatin assembly, and mismatch repair, have been identified in Saccharomyces cerevisiae. However, pathways that promote the formation of GCRs are not as well understood. Of these, the de novo telomere addition pathway and nonhomologous end-joining are the best characterized. Here, we demonstrate that defects in the mitotic checkpoint and the mitotic exit network can suppress GCRs in strains containing defects that increase the GCR rate. These data suggest that functional mitotic checkpoints can play a role in the formation of genome rearrangements.
总体染色体重排（GCRs）的积累是癌细胞的特征。在酿酒酵母中已鉴定出多种防止GCRs的途径，包括S期细胞周期检查点、同源重组、端粒维持、抑制端粒从头添加、染色质组装和错配修复。然而，促进GCRs形成的途径尚未得到很好的理解。其中，端粒从头添加途径和非同源末端连接是特征最明确的。在这里，我们证明有丝分裂检查点和有丝分裂退出网络中的缺陷可以抑制含有增加GCR率缺陷的菌株中的GCRs。这些数据表明功能性有丝分裂检查点可能在基因组重排的形成中起作用。
