Pregueiro António M, Liu Qiuyun, Baker Christopher L, Dunlap Jay C, Loros Jennifer J
Department of Genetics, Dartmouth Medical School, Hanover, NH 03755, USA.
Science. 2006 Aug 4;313(5787):644-9. doi: 10.1126/science.1121716. Epub 2006 Jun 29.
The clock gene period-4 (prd-4) in Neurospora was identified by a single allele displaying shortened circadian period and altered temperature compensation. Positional cloning followed by functional tests show that PRD-4 is an ortholog of mammalian checkpoint kinase 2 (Chk2). Expression of prd-4 is regulated by the circadian clock and, reciprocally, PRD-4 physically interacts with the clock component FRQ, promoting its phosphorylation. DNA-damaging agents can reset the clock in a manner that depends on time of day, and this resetting is dependent on PRD-4. Thus, prd-4, the Neurospora Chk2, identifies a molecular link that feeds back conditionally from circadian output to input and the cell cycle.
通过一个显示昼夜节律周期缩短和温度补偿改变的单一等位基因，鉴定出了粗糙脉孢菌中的生物钟基因period-4（prd-4）。随后的定位克隆和功能测试表明，PRD-4是哺乳动物检查点激酶2（Chk2）的直系同源物。prd-4的表达受生物钟调控，反之，PRD-4与生物钟组件FRQ发生物理相互作用，促进其磷酸化。DNA损伤剂可以根据一天中的时间重置生物钟，而这种重置依赖于PRD-4。因此，粗糙脉孢菌的Chk2即prd-4，确定了一个从昼夜节律输出到输入以及细胞周期进行条件性反馈的分子联系。
