Alternativni mehanizmi produžavanja telomera

undergraduate thesis

• Title (english): Alternative lenghtening of telomeres
• Author: Valentina Jurkaš
• Mentor: Maja Matulić (mentor)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2014, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Neograničen proliferativni kapacitet tumora i imortalnih staničnih linija ovisi o sposobnosti održavanja dužine telomera i obično se bazira na aktivaciji telomeraze, RNA-ovisne DNA polimeraze koja reverznom transkripcijom endogenog RNA kalupa sintetizira telomerna ponavljanja izravno na krajevima kromosoma. Međutim, znatan broj tumora može produživati telomere i bez prisutsva telomeraze mehanizmima alternativnog produžavanja telomera (ALT). Temelj ALT-a su replikacijski procesi ovisni o rekombinaciji kod kojih se kao kalup za sintezu dodatnih telomernih ponavljanja mogu koristiti druge telomere ili izvankromosomska telomerna ponavljanja, međutim molekularni procesi nisu razjašnjeni. Aktivnost ALT prepoznata je samo u nenormalnim stanicama i čini se da je njezino djelovanje usko povezano s poremećajem normalne funkcije telomera koja je primarno zaštita krajeva kromosoma kako ne bi bili zamijenjeni za dvolančane lomove nastale oštećenjem. Sukladno tome, samo produžavanje telomera posljedica je stalnog djelovanja stanične mašinerije za popravak na telomernu DNA. Mehanizmi održavanja telomera dobra su meta za razvoj antitumorskih tretmana: pojavljuju se u svim tumorima, većina zdravih stanica ih ne koristi i očekivane su nuspojave takvih tretmana minimalne. Većina istraživanja u tom smjeru provodi se na telomeraznim inhibitorima, međutim, da bi takvi tretmani zaista bili uspješni neophodno je da se u obzir uzme i ALT te da se bolje istraže mehanizmi i genetska podloga njegova djelovanja.

Abstract (english)

Unlimited proliferative capacity of tumor cells and immortal cell lines depends on their ability to maintain their telomeres, usually by activating telomerase, an RNA-dependent DNA polymerase that adds telomere repeats directly on the ends of chromosomes by reverse-transcribing an endogenous RNA template. On the other side, a number of tumors can also lengthen their telomeres without telomerase by means of alternative lengthening of telomeres (ALT). ALT is based on recombination-dependent replication processes that can use other telomeres or extrachromosomal telomeric repeats as templates for telomere elongation. Molecular basis of these processes are not yet clear. ALT activity has only been detected in abnormal cells and it seems that it is closely related to dysfunction in telomeres. These telomere dysfunctions compromise the roles they normally play in chromosome end protection and chromosomal ends are recognized as double stranded breaks caused by DNA damage. The telomere elongation itself is, by that definition, a consequence of cell repair machinery constantly acting on telomeric DNA. Telomere maintenance mechanisms could be used as a good target for cancer treatment because they appear in all tumors but not in healthy cells, so their inhibition should show minimal side-effects. Most research in that direction is based on telomerase inhibitors but for most successful results ALT also needs to be taken in consideration and its mechanisms and genetic background further investigated.

• Keywords: telomere; produžavanje telomera
• Keywords (english): telomeres; telomere elongation
• Language: croatian
• URN:NBN: urn:nbn:hr:217:100433
• 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: 2017-12-08 10:31:49