Parallel research on multiple model organisms shows that while some principles of telomere biology are conserved among all eukaryotic kingdoms, we also find some deviations that reflect different evolutionary paths and life strategies, which may have diversified after the establishment of telomerase as a primary mechanism for telomere maintenance. Much more than animals, plants have to cope with environmental stressors, including genotoxic factors, due to their sessile lifestyle. This is, in principle, made possible by an increased capacity and efficiency of the molecular systems ensuring maintenance of genome stability, as well as a higher tolerance to genome instability. Furthermore, plant ontogenesis differs from that of animals in which tissue differentiation and telomerase silencing occur during early embryonic development, and the "telomere clock" in somatic cells may act as a preventive measure against carcinogenesis. This does not happen in plants, where growth and ontogenesis occur through the serial division of apical meristems consisting of a small group of stem cells that generate a linear series of cells, which differentiate into an array of cell types that make a shoot and root. Flowers, as generative plant organs, initiate from the shoot apical meristem in mature plants which is incompatible with the human-like developmental telomere shortening. In this review, we discuss differences between human and plant telomere biology and the implications for aging, genome stability, and cell and organism survival. In particular, we provide a comprehensive comparative overview of telomere proteins acting in humans and in Arabidopsis thaliana model plant, and discuss distinct epigenetic features of telomeric chromatin in these species.

• Klíčová slova
• Arabidopsis, aging, chromatin, epigenetics, human, review, telomerase, telomere,
• MeSH
• chromatin metabolismus   MeSH
• epigeneze genetická MeSH
• lidé MeSH
• rostliny metabolismus   MeSH
• stárnutí buněk genetika   MeSH
• telomerasa metabolismus   MeSH
• telomery metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• chromatin MeSH
• telomerasa MeSH

The semiconservative replication of telomeres is facilitated by the shelterin component TRF1. Without TRF1, replication forks stall in the telomeric repeats, leading to ATR kinase signaling upon S-phase progression, fragile metaphase telomeres that resemble the common fragile sites (CFSs), and the association of sister telomeres. In contrast, TRF1 does not contribute significantly to the end protection functions of shelterin. We addressed the mechanism of TRF1 action using mouse conditional knockouts of BLM, TRF1, TPP1, and Rap1 in combination with expression of TRF1 and TIN2 mutants. The data establish that TRF1 binds BLM to facilitate lagging but not leading strand telomeric DNA synthesis. As the template for lagging strand telomeric DNA synthesis is the TTAGGG repeat strand, TRF1-bound BLM is likely required to remove secondary structures formed by these sequences. In addition, the data establish that TRF1 deploys TIN2 and the TPP1/POT1 heterodimers in shelterin to prevent ATR during telomere replication and repress the accompanying sister telomere associations. Thus, TRF1 uses two distinct mechanisms to promote replication of telomeric DNA and circumvent the consequences of replication stress. These data are relevant to the expression of CFSs and provide insights into TIN2, which is compromised in dyskeratosis congenita (DC) and related disorders.

• Klíčová slova
• BLM, G quadruplex, TRF1, replication, shelterin, telomere,
• MeSH
• aktivace enzymů MeSH
• ATM protein metabolismus   MeSH
• DNA vazebné proteiny metabolismus   MeSH
• genový knockout MeSH
• helikasy RecQ genetika   metabolismus   MeSH
• kultivované buňky MeSH
• mikrosatelitní repetice genetika   MeSH
• mutace MeSH
• protein TRF1 genetika   metabolismus   MeSH
• proteiny vázající telomery genetika   metabolismus   MeSH
• replikace DNA genetika   MeSH
• serinové proteasy genetika   metabolismus   MeSH
• shelterinový komplex MeSH
• signální transdukce MeSH
• telomery genetika   MeSH
• vazba proteinů MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• Acd protein, mouse MeSH Prohlížeč
• ATM protein MeSH
• Atr protein, mouse MeSH Prohlížeč
• Bloom syndrome protein MeSH Prohlížeč
• DNA vazebné proteiny MeSH
• helikasy RecQ MeSH
• POT1 protein, mouse MeSH Prohlížeč
• protein TRF1 MeSH
• proteiny vázající telomery MeSH
• serinové proteasy MeSH
• shelterinový komplex MeSH
• Tinf2 protein, mouse MeSH Prohlížeč

The past decade has witnessed an explosion of knowledge concerning the structure and function of chromosome terminal structures-telomeres. Today's telomere research has advanced from a pure descriptive approach of DNA and protein components to an elementary understanding of telomere metabolism, and now to promising applications in medicine. These applications include 'passive' ones, among which the use of analysis of telomeres and telomerase (a cellular reverse transcriptase that synthesizes telomeres) for cancer diagnostics is the best known. The 'active' applications involve targeted downregulation or upregulation of telomere synthesis, either to mortalize immortal cancer cells, or to rejuvenate mortal somatic cells and tissues for cellular transplantations, respectively. This article reviews the basic data on structure and function of human telomeres and telomerase, as well as both passive and active applications of human telomere biology.

• MeSH
• antitumorózní látky farmakologie   MeSH
• buněčná diferenciace MeSH
• buněčné dělení MeSH
• lidé MeSH
• nádory enzymologie   genetika   patologie   MeSH
• regulace genové exprese enzymů MeSH
• stárnutí genetika   MeSH
• telomerasa analýza   antagonisté a inhibitory   genetika   metabolismus   MeSH
• telomery chemie   enzymologie   fyziologie   MeSH
• tkáňové inženýrství MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• antitumorózní látky MeSH
• telomerasa MeSH