Zakian V A
Dept of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
Trends Cell Biol. 1996 Jan;6(1):29-33. doi: 10.1016/0962-8924(96)81035-x.
Telomeres are specialized DNA protein structures that form the ends of eukaryotic chromosomes. In yeast, loss of even a single telomere causes a prolonged, but transitory, cell-cycle arrest. During this arrest, many broken chromosomes acquire a new telomere by one of three pathways, although at the cost of a partial loss of heterozygosity. In addition, a substantial fraction of the chromosomes lacking a telomere is lost, which generates an aneuploid cell. In these cases, the broken chromosome is usually replicated and segregated for ten or more cell divisions in unstable form. Extrapolation from yeast suggests that the gradual loss of telomeric DNA that accompanies ageing in humans may initiate the kinds of chromosomal rearrangements and genetic changes that are associated with tumorigenesis.
端粒是形成真核染色体末端的特殊DNA蛋白质结构。在酵母中,即使单个端粒的缺失也会导致细胞周期延长但短暂的停滞。在这种停滞期间,许多断裂的染色体通过三种途径之一获得新的端粒,尽管代价是杂合性部分丧失。此外,相当一部分缺乏端粒的染色体会丢失,从而产生非整倍体细胞。在这些情况下,断裂的染色体通常以不稳定的形式复制并分离十次或更多次细胞分裂。从酵母中推断,人类衰老过程中端粒DNA的逐渐丢失可能引发与肿瘤发生相关的各种染色体重排和基因变化。