Telomere – čimbenici genetičke nestabilnosti

undergraduate thesis

• Title (english): Telomeres – the factors of genetic instability
• Author: Damira Veseljak
• Mentor: Nada Oršolić (mentor)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2017-09-13, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Kako bi se od razaranja i mehanizama popravka dvolančanih lomova zaštitili linearni eukariotski kromosomi, na njihovim se krajevima nalaze telomere - specifične DNA – proteinske strukture sastavljene od ponavljajućih TTAGGG sljedova nukleotida. Zbog prirode replikacije DNA svakom diobom dolazi do skraćivanja telomera te je konačan broj dioba određen duljinom telomera. Kratke su telomere čimbenici genetičke nestabilnosti. Najveći je uzrok te nestabilnosti ciklus lom-fuzija- most (B/F/B) koji dovodi do nerecipročnih translokacija, fragmentacije DNA i duplikacija cijelog kromosoma ili genoma. Stanice smrt uzrokovanu kratkim telomerama mogu izbjeći reaktivacijom telomeraze, RNA-ovisne DNA polimeraze koja je inače aktivna u embrionalnim stanicama, ili alternativnim mehanizmima produljenja telomera (ALT). U uvjetima in vitro reaktivacija telomeraze dovodi do imortalizacije stanica dok je in vivo velik čimbenik razvoja tumora. Telomeraza je aktivna u preko 90% svih tumora, a neaktivna u normalnim i zdravim somatskim stanicama. Inhibitori telomeraze zbog toga daju brojne mogućnosti u razvoju anti-tumorskih lijekova.

Abstract (english)

To avoid degradation and the mechanisms of DNA double strain break repair, linear eukaryotic chromosomes have developed telomeres – the specific DNA-protein structures comprised of repetitive TTAGGG nucleotide sequences. Due to the nature of DNA replication every division makes telomeres shorter. Because of this, the number of divisions is set by telomere length. Short telomeres are factors of genetic instability. The most significant cause of genetic instability lies in the fusion-bridge-fusion cycle (B/F/B) which leads to nonreciprocal translocations, DNA fragmenting and duplications of the whole chromosome or even genome. Cells can escape death caused by short telomeres by reactivation of telomerase, RNA-dependent DNA polymerase usually active only in embryotic cells, or by the alternative lengthening of telomeres (ALT). In vitro reactivation of telomerase leads to cell immortalization while in vivo active telomerase means tumour development. Telomerase is active in over 90% of all tumours and inactive in normal healthy somatic cells. Because of this, telomerase inhibitors play a crucial role in the development of anti-cancer therapeutics.

• Keywords: telomere; genetička nestabilnost
• Keywords (english): telomeres; genetic instability
• Language: croatian
• URN:NBN: urn:nbn:hr:217:180976
• Study programme: Title: Molecular Biology; Study programme type: university; Study level: undergraduate; Academic / professional title: sveučilišni/a prvostupnik/prvostupnica (baccalaureus/baccalaurea) molekularne biologije (sveučilišni/a prvostupnik/prvostupnica (baccalaureus/baccalaurea) molekularne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2017-09-19 08:34:34