126 KB31 KB199420252000Cör, AndrejGale, NinaLuzar, BoštjanPoljak, Marioštevilka:3letnik:39str. 271-279ISSN:0025-8121COBISSID:13017305URN:URN:NBN:SI:doc-6LEXFTLQslMedicinski razglediMedicinski razglediCell deathChemistryEtiologyGenes, cdcMetabolismMutagenesisMutationNeoplasmsPhysiologyTelomeraseTelomereTelomere in telomeraza pri človeku - zgradba, funkcija in vloga v procesu kancerogeneze| Human telemore and telomerase: structure, function and role in cancerogenesis|With each somatic cell division; the chromosomal ends, or telomeres, progressively shorten. Critically shortened telomeres are recognised by DNA repair systems as DNA damage, the cells are withdrawn from the cell cycle, senesce and eventually die. Mutations in the genes responsible for cell division cycle control, or repression of their protein products, enable cells to continue their proliferation. In the period of the so-called extended life span the cells acquire additional genetic mutations, telomeres progressively shorten, and genomic instability increases. Due to the extremely shortened telomeres accompanied by accumulation of genetic abnormalities and increased genomic instability, most cells enter the period of crisis and die. Those cells that can preveni telomere shortening escape crisis and continue to proliferate. Due to the stabilised telomeres they have the ability to proliferate indefinitely. The only known mechanism so far by which human cellscan regulate the length of telomeres is by the action of the enzyme telomerase. Detection of telomexase activity in the overwhelming majority of advanced and metastatic human cancer but not in most somatic cells implies that telomerase dependent mmorEalization could contribute to the development of malignancy. Thus, repression of telomerase activity may be a novel adjuvanttherapy for the treatment of human cancer and detection of telomerase activity may be important for cancer diagnostic. In the present review we havedescribed the most recent advances in the field of telomeres and telomere related proteins, the so-called telomeric complex, its structure and function.Furthermore, we have also outlined the structure, function and mechanisms, by which telomerase regulates the length of human telomeres. Finally, the current views on the role of telomerase in human cancerogenesis are presentedZ vsako celično delitvijo se telomere človeških somatskih celic skrajšajo. Kritično kratke telomere celični popravljalni mehanizmi spoznajo kot okvarjenoDNA in zaustavijo celično delitev. Celice vstopijo v obdobje staranjain odmrejo. Mutacije v genih, ki uravnavajo celično delitev, oziroma motnje v delovanju njihovih beljakovinskih, pridelkov, omogočijo tako spremenjenim celicam nadaljevanje delitev. V obdobju podaljšane življenjske dobe celice lahko pridobijo dodatne genetske napake, telomere se še naprej krajšajo in genomska nestabilnost se povečuje. Zaradi izrazitega skrajšanja telomer, kopičenja genetskih napak in povečevanja genomske nestabilnosti večina celic vstopi v fazo krize in odmre. Celice, ki krajšanje telomer preprečijo, obdobje krize preživijo. Take celice so nesmrtne, saj imajo zaradiuravnavane dolžine telomer neomejeno možnost proliferacije. Encim telomeraza nadomesti izgubo telomer z njihovo ponovno sintezo in je do sedaj edini znani mehanizem uravnavanja dolžine telomer pri človeku. Večina normalnih somatskih celic nima dokazljive telomerazne aktivnosti, njena ponovna aktivacija pa je dokazljiva v več kot 85 % malignih tumorjev. Razliko v telomerazni aktivnosti med tumorskim tkivom in normalnimi tkivi bi zato lahko uporabili v diagnostiki malignih obolenj in pri načrtovanju novih načinov zdravljenja malignih tumorjev. V prispevku so opisana najnovejša spoznanja o telomernem kompleksu, njegovi zgradbi in delovanju pri človeku. Prikazana je zgradba, vloga in mehanizem delovanja telomeraze ter njen pomen vprocesu kancerogeneze pri človekuTEXTznanstveno časopisjejournalsSlovenian National E-content AggregatorNational and University Library of SloveniaDruštvo Medicinski razgledi