Rowley R, Subramani S, Young P G
Department of Radiology, University of Utah Medical Center, Salt Lake City 84132.
EMBO J. 1992 Apr;11(4):1335-42. doi: 10.1002/j.1460-2075.1992.tb05178.x.
'Checkpoint' controls ensure that the events of the cell cycle are completed in an orderly fashion. For example, such controls delay mitosis until DNA synthesis and repair of radiation-induced DNA damage are complete. The rad series of radiosensitive fission yeast mutants was examined to identify strains deficient for the DNA damage-responsive checkpoint control. Five were identified. A characterization of one (rad1-1) and the wild-type is presented. The rad1-1 mutant does not arrest after irradiation, is sensitive to killing by radiation and is not arrested by hydroxyurea, and thus is also deficient for the DNA synthesis-responsive checkpoint control. The radiosensitivity of the rad1-1 mutant was greatly reduced when irradiated and maintained for 6 h in a non-dividing (density inhibited) state, demonstrating that rad1-1 is repair proficient and radiosensitive only through failure to delay. The checkpoint controls for which rad1 is required appear to regulate G2-M progression through the activity of cdc2, here implicated in this role by the coincidence of the radiation transition point and the cdc2 execution point.
“关卡”控制确保细胞周期事件按顺序完成。例如，此类控制会延迟有丝分裂，直到DNA合成以及辐射诱导的DNA损伤修复完成。研究了对辐射敏感的裂殖酵母突变体的rad系列，以鉴定DNA损伤反应性关卡控制缺陷的菌株。鉴定出了5个。本文介绍了其中一个（rad1-1）与野生型的特征。rad1-1突变体在辐照后不会停滞，对辐射杀伤敏感，并且不会被羟基脲阻滞，因此在DNA合成反应性关卡控制方面也存在缺陷。当rad1-1突变体在非分裂（密度抑制）状态下辐照并维持6小时后，其辐射敏感性大大降低，这表明rad1-1修复能力正常，只是由于未能延迟才对辐射敏感。rad1所需的关卡控制似乎通过cdc2的活性来调节G2-M期进程，此处辐射转变点与cdc2执行点的重合表明cdc2参与了这一作用。
