Holliday R
CSIRO Division of Biomolecular Engineering, North Ryde, NSW, Sydney, Australia.
Bioessays. 1996 Jan;18(1):3-5. doi: 10.1002/bies.950180103.
The replication of linear chromosome DNA by DNA polymerase leads to the loss of terminal sequences, in the absence of a special mechanism to maintain ends or telomeres. This mechanism is known to consist of short terminal repeats and the enzyme telomerase, which contains RNA complementary to the DNA repeats. There is evidence that telomeric DNA continually decreases in size in the absence of telomerase, and this is followed by cellular senescence. Immortalisation of somatic cells is accompanied, at least in some cases, by acquisition of telomerase activity. The cloning of DNA coding for the RNA component of telomerase has opened up some new experimental approaches, including the study of telomerases with mutant RNA. The telomere theory of cellular senescence appears to provide a molecular basis for the 'Hayflick limit' to human fibroblast growth. However the telomeres and behaviour of primary mouse cells are anomolous, and many immortalised human cell lines lack normal telomerase activity. These exceptions are not easily accommodated in the telomere theory.
在缺乏维持末端或端粒的特殊机制时，DNA聚合酶对线性染色体DNA的复制会导致末端序列的丢失。已知这种机制由短末端重复序列和端粒酶组成，端粒酶含有与DNA重复序列互补的RNA。有证据表明，在缺乏端粒酶的情况下，端粒DNA的大小会持续减小，随后细胞会发生衰老。体细胞的永生化，至少在某些情况下，伴随着端粒酶活性的获得。编码端粒酶RNA组分的DNA的克隆开辟了一些新的实验方法，包括对具有突变RNA的端粒酶的研究。细胞衰老的端粒理论似乎为人类成纤维细胞生长的“海弗利克极限”提供了分子基础。然而，原代小鼠细胞的端粒和行为是异常的，而且许多永生化的人类细胞系缺乏正常的端粒酶活性。这些例外情况不易纳入端粒理论。
