A conserved checkpoint pathway mediates DNA damage-induced apoptosis and cell cycle arrest in C. elegans
A conserved checkpoint pathway mediates DNA damage-induced apoptosis and cell cycle arrest in C. elegans
复制标题
DOI：
10.1016/s1097-2765(00)80438-4
复制
发表时间：
2000-03-01
期刊：
影响因子：
16
通讯作者：
Hengartner, MO
中科院分区：
文献类型：
--
作者：
Gartner, A;Milstein, S;Hengartner, MO
为了在 DNA 损伤后维持基因组稳定性，多细胞生物会激活诱导细胞周期停滞或凋亡的检查点。在这里，我们发现，在线虫秀丽隐杆线虫中，基因毒性应激会阻碍细胞增殖并诱导生殖细胞凋亡。重组中间体的积累同样会导致受影响细胞的死亡。检查点诱导的细胞凋亡由核心细胞凋亡机制 (CED-S/CED-4/CED-3) 介导，但在遗传上不同于体细胞死亡和生理性生殖细胞死亡。三个基因的突变——mrt-2（编码粟酒裂殖酵母rad1检查点基因的线虫同源物）、rad-5和him-7——阻断了DNA损伤诱导的细胞凋亡和细胞增殖停滞。我们的结果表明 rad1 同源物与 DNA 损伤诱导的动物细胞凋亡有关。
To maintain genomic stability following DNA damage, multicellular organisms activate checkpoints that induce cell cycle arrest or apoptosis. Here we show that genotoxic stress blocks cell proliferation and induces apoptosis of germ cells in the nematode C. elegans. Accumulation of recombination intermediates similarly leads to the demise of affected cells. Checkpoint-induced apoptosis is mediated by the core apoptotic machinery (CED-S/CED-4/CED-3) but is genetically distinct from somatic cell death and physiological germ cell death. Mutations in three genes-mrt-2, which encodes the C. elegans homolog of the S. pombe rad1 checkpoint gene, rad-5, and him-7-block both DNA damage-induced apoptosis and cell proliferation arrest. Our results implicate rad1 homologs in DNA damage-induced apoptosis in animals.