TELOMERE RESEARCH

Telomere Research

Telomere Research

Introduction

Telomeres, the nucleoprotein “caps” protecting the ends of linear chromosomes, are maintained by telomerase. Division-dependent telomere shortening correlating with age initiates senescence on a cellular grade and telomere dysfunction can facilitate oncogenesis. Therefore, the study of telomere biology is critical to the comprehending of aging and cancer. The mouse has been used extensively as a model for human telomere biology. However, there are fundamental differences between mouse and human cells which make the mouse less than optimal as a paradigm for the study of telomeres and telomerase. (McClintock, 1939) Other model systems should be characterized, refined and promoted to facilitate new developments in aging research. The chicken, a classic model for the study of developmental biology, possesses a telomere genome with highly conserved aspects and distinctive features which make it uniquely suited for the study of telomere maintenance mechanisms, their function and dysfunction. The benefits of the chicken telomere genome as a model are enhanced by the existence of chicken cell lines and genetic lines which exhibit unique variations in the distribution and heterogeneity of telomeric DNA arrays as well as diversity in telomerase activity profiles and expression of telomerase components. (Lundblad, 1989) The reason of this review is to focus the chicken as a form for aging study, expressly as a form for telomere and telomerase research, and to boost its utility as such by recounting expansion in the study of chicken telomeres and telomerase in the context of associated improvement in human and mouse.

Telomerase convoluted composition, assembly and regulation

While human telomerase was discovered in 1989, the full composition of the enzyme has stayed undetermined. Moreover, the pathways of telomerase biosynthesis and recruitment at telomeres are still far from being clearly understood. (Lingner, 1997) One of the reasons is that the cellular allowance of the enzyme is amazingly uncommon, with perhaps as couple of as 20 substances contained in each cell. However, lately one other component, dyskerin has been identified in supplement to the telomerase RNA and the hTERT protein. Dyskerin is an RNA binding protein that is renowned to bind to numerous distinct RNAs. Also affiliated to the telomerase convoluted, the ATPase pontin and reptin appear to be necessary for telomerase assembly. The next step which is not going to be an very simple one will be the x-crystallography to work out the 3D structure of the purposeful enzyme. (Hayflick, 1965)

Lessons from yeast show that the telomerase activity at telomere is tightly coupled to cell cycle and require its interaction with proteins binding the 3' tails of chromosome ends. The mean by which mammalian telomerase is employed to telomeres profited recent insight by the breakthrough that the telomerase complex require to be associated to constituents of the Cajal bodies to be consigned to chromosome ends. The factors involved in the binding of the mammalian telomerase to telomeric DNA are still unknown but proteins binding to the 3' tails (including Pot1 and Tpp1) are likely candidates. (Hayflick, 1961)

Telomeric chromatin

It has been a longstanding concept that telomeres are ...