Olovnikov A M
Institute of Biochemical Physics, Russian Academy of Sciences, Moscow, Russia.
Exp Gerontol. 1996 Jul-Aug;31(4):443-8. doi: 10.1016/0531-5565(96)00005-8.
In 1971 I published a theory in which I first formulated the DNA end replication problem and explained how it could be solved. The solution to this problem also provided an explanation for the Hayflick Limit, which underpins the discovery of in vitro and in vivo cell senescence. I proposed that the length of telomeric DNA, located at the ends of chromosomes consists of repeated sequences, which play a buffer role and should diminish in dividing normal somatic cells at each cell doubling. I also proposed that the loss of sequences containing important information that could occur after buffer loss could cause the onset of cellular senescence. I also suggested that for germline cells and for the cells of vegetatively propagated organisms and immortal cell populations like most cancer cell lines, an enzyme might be activated that would prevent the diminution of DNA termini at each cell division, thus protecting the information containing part of the genome. In the last few years, most of my suggestions have been authenticated by laboratory evidence. the DNA sequences that shorten in dividing normal cells are telomeres and the enzyme that maintains telomere length constant in immortal cell populations is telomerase.
1971年，我发表了一种理论，首次阐述了DNA末端复制问题，并解释了该问题的解决方式。该问题的解决方案也为海弗利克极限提供了解释，而海弗利克极限是体外和体内细胞衰老发现的基础。我提出，位于染色体末端的端粒DNA长度由重复序列组成，这些重复序列起到缓冲作用，在正常体细胞每次倍增时应会缩短。我还提出，缓冲序列丢失后可能发生的重要信息序列丢失会导致细胞衰老的开始。我还指出，对于生殖细胞、无性繁殖生物体的细胞以及大多数癌细胞系等永生细胞群体而言，可能会激活一种酶，该酶可防止每次细胞分裂时DNA末端缩短，从而保护基因组中包含信息的部分。在过去几年中，我的大部分观点已得到实验室证据的证实。在正常分裂细胞中缩短的DNA序列是端粒，而在永生细胞群体中维持端粒长度恒定的酶是端粒酶。
