When and How Telomeres Lengthen in Development and Cell Lines: Evolution of Olovnikov’s Telomere Theory

Abstract

Telomeres are special nucleoprotein structures that protect the ends of linear chromosomes. Telomeric DNA is composed of 6-nucleotide repeats that are synthesized by telomerase, a specialized DNA polymerase. According to Alexey Olovnikov’s telomere theory of aging, replicative aging in somatic cells is caused by telomere shortening during cell division. Even before telomerase was discovered, he predicted in 1973 that telomere elongation occurs only in certain types of cells, such as germ cells, stem cells, and tumor cells. In this review, we explore the stages of animal ontogenesis where telomere elongation takes place and the mechanisms of telomere maintenance during gametogenesis and embryogenesis. The mechanism of homologous recombination that controls telomere length tuning during early embryogenesis is discussed. The advancement of modern cell technologies, including those based on induced pluripotent stem cells, inevitably raises the issue of genome stability in clinically relevant cell lines. Here we compare telomere maintenance mechanisms in embryonic and induced pluripotent stem cells, as well as discuss how telomere stability can be influenced during development.