Kitazono A, Matsumoto T
Department of Radiation Oncology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Bioessays. 1998 May;20(5):391-9. doi: 10.1002/(SICI)1521-1878(199805)20:5<391::AID-BIES6>3.0.CO;2-R.
Checkpoints maintain the interdependency of cell cycle events by permitting the onset of an event only after the completion of the preceding event. The DNA replication checkpoint induces a cell cycle arrest until the completion of the DNA replication. Similarly, the DNA damage checkpoint arrests cell cycle progression if DNA repair is incomplete. A number of genes that play a role in the two checkpoints have been identified through genetic studies in yeasts, and their homologues have been found in fly, mouse, and human. They form signaling cascades activated by a DNA replication block or DNA damage and subsequently generate the negative constraints on cell cycle regulators. The failure of these signaling cascades results in producing offspring that carry mutations or that lack a portion of the genome. In humans, defects in the checkpoints are often associated with cancer-prone diseases. Focusing mainly on the studies in budding and fission yeasts, we summarize the recent progress.
细胞周期检验点通过仅在前一事件完成后才允许下一事件的发生来维持细胞周期事件的相互依赖性。DNA复制检验点会诱导细胞周期停滞,直到DNA复制完成。同样,如果DNA修复不完全,DNA损伤检验点会阻止细胞周期进程。通过对酵母的遗传学研究,已经鉴定出了一些在这两个检验点中起作用的基因,并且在果蝇、小鼠和人类中也发现了它们的同源物。它们形成由DNA复制阻滞或DNA损伤激活的信号级联反应,随后对细胞周期调节因子产生负向调控。这些信号级联反应的失败会导致产生携带突变或缺少部分基因组的后代。在人类中,检验点缺陷通常与易患癌症的疾病有关。本文主要聚焦于芽殖酵母和裂殖酵母的研究,总结了近期的进展。