Neff M W, Burke D J
Department of Biology, University of Virginia, Charlottesville 22901.
Mol Cell Biol. 1992 Sep;12(9):3857-64. doi: 10.1128/mcb.12.9.3857-3864.1992.
Dicentric chromosomes are genetically unstable and depress the rate of cell division in Saccharomyces cerevisiae. We have characterized the effects of a conditionally dicentric chromosome on the cell division cycle by using microscopy, flow cytometry, and an assay for histone H1 kinase activity. Activating the dicentric chromosome induced a delay in the cell cycle after DNA replication and before anaphase. The delay occurred in the absence of RAD9, a gene required to arrest cell division in response to DNA damage. The rate of dicentric chromosome loss, however, was elevated in the rad9 mutant. A mutation in BUB2, a gene required for arrest of cell division in response to loss of microtubule function, diminished the delay. Both RAD9 and BUB2 appear to be involved in the cellular response to a dicentric chromosome, since the conditionally dicentric rad9 bub2 double mutant was highly inviable. We conclude that a dicentric chromosome results in chromosome breakage and spindle aberrations prior to nuclear division that normally activate mitotic checkpoints, thereby delaying the onset of anaphase.
双着丝粒染色体在遗传上不稳定，并降低酿酒酵母中的细胞分裂速率。我们通过显微镜检查、流式细胞术以及组蛋白H1激酶活性测定，对条件性双着丝粒染色体对细胞分裂周期的影响进行了表征。激活双着丝粒染色体在DNA复制后和后期之前诱导细胞周期延迟。该延迟在缺乏RAD9的情况下发生，RAD9是响应DNA损伤而阻止细胞分裂所需的基因。然而，在rad9突变体中双着丝粒染色体丢失的速率升高。BUB2发生突变，BUB2是响应微管功能丧失而阻止细胞分裂所需的基因，该突变减少了延迟。RAD9和BUB2似乎都参与了细胞对双着丝粒染色体的反应，因为条件性双着丝粒rad9 bub2双突变体高度不可存活。我们得出结论，双着丝粒染色体在核分裂之前导致染色体断裂和纺锤体畸变，这通常会激活有丝分裂检查点，从而延迟后期的开始。
