Zhivotovsky Boris, Kroemer Guido
Institute of Environmental Medicine, Karolinska Institutet, Box 210, Nobels väg 13, SE-171 77 Stockholm, Sweden.
Nat Rev Mol Cell Biol. 2004 Sep;5(9):752-62. doi: 10.1038/nrm1443.
Genomic instability is intrinsically linked to significant alterations in apoptosis control. Chromosomal and microsatellite instability can cause the inactivation of pro-apoptotic pathways. In addition, the inhibition of apoptosis itself can be permissive for the survival and ongoing division of cells that have failed to repair DNA double-strand breaks, experience telomere dysfunction or are in an abnormal polyploid state. Furthermore, DNA-repair proteins can regulate apoptosis. So, genomic instability and apoptosis are intimately linked phenomena, with important implications for the pathophysiology of cancer.
基因组不稳定与细胞凋亡调控的显著改变存在内在联系。染色体和微卫星不稳定可导致促凋亡途径失活。此外，细胞凋亡本身受到抑制，可能会使那些未能修复DNA双链断裂、经历端粒功能障碍或处于异常多倍体状态的细胞存活并持续分裂。此外，DNA修复蛋白可调节细胞凋亡。因此，基因组不稳定和细胞凋亡是密切相关的现象，对癌症的病理生理学具有重要意义。
