Telomeres as dynamic structures of human genome: the effect of endogenous and exogenous factors

Abstract

In this review, we summarize data on the structural and functional characteristics of human telomeres and analyze how endo- and exogenous factors influence telomere length. We elucidate the history of telomere investigation, describe their structure and functions, methods of their study. We also characterize the mechanisms of telomere lengthening and shortening. We discuss in detail endo- and exogenous factors affecting telomere length during gametogenesis, embryogenesis and in the postnatal period of human development. We describe how oxidative stress influences telomere length through guanine oxidation, single-strand breaks in DNA, decrease of telomerase activity and suppression of recombination in telomeric sequences. We conclude that the multidirectional effect of various factors, both sporadic and determined by the developmental program, ensures the dynamic equilibrium of telomere length. A shift in this balance due to increased influence of one or several factors can lead to telomere lengthening or shortening. Understanding the mechanisms underlying the telomere length changes and the critical periods of exposure to both protective and negative factors is important to contribute to the knowledge about telomere functions and to develop approaches of telomere length correction.