Walworth N, Davey S, Beach D
Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, New York 11724.
Nature. 1993 May 27;363(6427):368-71. doi: 10.1038/363368a0.
The dependence of cell-cycle progression on the integrity of the genome has been described as checkpoint control. A number of mutants of the fission yeast Schizosaccharomyces pombe, selected for their sensitivity to DNA damage caused by radiation (rad mutants) or to the DNA synthesis inhibitor hydroxyurea (hus mutants) have been classified as checkpoint mutants because they fail to arrest the cell cycle in response to DNA damage or incompletely replicated DNA. Coupling of the checkpoint pathways that monitor DNA repair and replication to control of the cell cycle is essential. In a search for components that interact with the cell-cycle regulatory kinase p34cdc2, we have identified a novel fission yeast protein kinase homologue which is involved in cell-cycle arrest when DNA damage has occurred or when unligated DNA is present. We have called the gene encoding this protein chk1 for checkpoint kinase. Multiple copies of chk1 partially rescue the ultraviolet sensitivity of rad1-1, a mutant deficient in checkpoint control. Identification of a gene involved in checkpoint control as a rescue of a cdc2 mutant links the rad1-dependent DNA-damage-sensing pathway and p34cdc2 activity.
细胞周期进程对基因组完整性的依赖性已被描述为关卡控制。裂殖酵母粟酒裂殖酵母的许多突变体，因其对辐射引起的DNA损伤（rad突变体）或DNA合成抑制剂羟基脲（hus突变体）敏感而被挑选出来，这些突变体已被归类为关卡突变体，因为它们在DNA损伤或DNA复制不完全时无法使细胞周期停滞。监测DNA修复和复制的关卡途径与细胞周期控制的耦合至关重要。在寻找与细胞周期调节激酶p34cdc2相互作用的成分时，我们鉴定出一种新的裂殖酵母蛋白激酶同源物，当发生DNA损伤或存在未连接的DNA时，它参与细胞周期停滞。我们将编码这种蛋白的基因称为chk1，即关卡激酶。chk1的多个拷贝部分挽救了rad1-1的紫外线敏感性，rad1-1是一种缺乏关卡控制的突变体。将一个参与关卡控制的基因鉴定为对cdc2突变体具有挽救作用，这将rad1依赖性DNA损伤感应途径与p34cdc2活性联系起来。
