prikaz prve stranice dokumenta The repair of Topoisomerase 1 and 2 DNA-protein crosslinks in vivo
Embargo period 2024-11-17
doctoral thesis
The repair of Topoisomerase 1 and 2 DNA-protein crosslinks in vivo
Zagreb: University of Zagreb, Faculty of Science, 2023. urn:nbn:hr:217:039955
Antičević, Ivan
University of Zagreb
Faculty of Science
Department of Biology

Institutional repository: Repository of the Faculty of Science

Cite this document

Antičević, I. (2023). The repair of Topoisomerase 1 and 2 DNA-protein crosslinks in vivo (Doctoral thesis). Zagreb: University of Zagreb, Faculty of Science. Retrieved from https://urn.nsk.hr/urn:nbn:hr:217:039955

Antičević, Ivan. "The repair of Topoisomerase 1 and 2 DNA-protein crosslinks in vivo." Doctoral thesis, University of Zagreb, Faculty of Science, 2023. https://urn.nsk.hr/urn:nbn:hr:217:039955

Antičević, Ivan. "The repair of Topoisomerase 1 and 2 DNA-protein crosslinks in vivo." Doctoral thesis, University of Zagreb, Faculty of Science, 2023. https://urn.nsk.hr/urn:nbn:hr:217:039955

Antičević, I. (2023). 'The repair of Topoisomerase 1 and 2 DNA-protein crosslinks in vivo', Doctoral thesis, University of Zagreb, Faculty of Science, accessed 08 May 2024, https://urn.nsk.hr/urn:nbn:hr:217:039955

Antičević I. The repair of Topoisomerase 1 and 2 DNA-protein crosslinks in vivo [Doctoral thesis]. Zagreb: University of Zagreb, Faculty of Science; 2023 [cited 2024 May 08] Available at: https://urn.nsk.hr/urn:nbn:hr:217:039955

I. Antičević, "The repair of Topoisomerase 1 and 2 DNA-protein crosslinks in vivo", Doctoral thesis, University of Zagreb, Faculty of Science, Zagreb, 2023. Available at: https://urn.nsk.hr/urn:nbn:hr:217:039955

Metadata
TitleThe repair of Topoisomerase 1 and 2 DNA-protein crosslinks in vivo
Title (croatian)Popravak križnih veza između DNA i topoizomeraza 1 i 2
AuthorIvan Antičević
MentorMarta Popović (mentor)
Committee memberTvrtko Smital (predsjednik povjerenstva)
Committee memberDragomira Majhen (član povjerenstva)
Committee memberMarko Močibob (član povjerenstva)
GranterUniversity of Zagreb
Faculty of Science
(Department of Biology)
Zagreb
Defense date and country2023-11-17, Croatia
Scientific / art field,
discipline and subdiscipline		NATURAL SCIENCES
Biology
Universal decimal classification
(UDC)		577 - Biochemistry. Molecular biology. Biophysics
Abstract
DNA-protein crosslinks (DPCs) are frequent and damaging DNA lesions that affect all DNA transactions, which can lead to the formation of DSBs (double-strand DNA breaks), genomic instability and cell death. At the organismal level, impaired DPC repair (DPCR) is associated with cancer, aging, and neurodegeneration. Repair of the two most abundant enzymatic DPCs, involving topoisomerase 1 and 2 was studied in cell models, but data from organisms are still limited. Here, using a zebrafish model and human cells, we show that endogenous TOP1-DPCs are repaired by TDP1 and SPRTN through independent pathways. Notably, chemically induced TOP1-DPCs, using camptothecin or formaldehyde, require an epistatic action of both enzymes, and effectively prevent the accumulation of TOP1-DPC-related damage. Furthermore, we identified the zebrafish Tdp2 orthologue, Tdp2b, as the enzyme responsible for the removal of Top2-DPC residues. Reduced Tdp2 function, observed in both, living organisms and cellular models, causes significant phenotypic changes. This study provides the first insights into the repair of TOP1- and TOP2-DPCs in vivo.
Abstract (croatian)
Križne veze proteina i DNA (eng. DPCs) su česte i štetne lezije DNA koje ometaju sve procese na DNA, što može dovesti do pojave dvostrukih lomova, genomske nestabilnosti i stanične smrti. Na razini organizma, neefikasan popravak križnih veza proteina i DNA povezan je s nastankom tumora, starenjem i neurodegeneracijom. Dok je popravak najčešćih enzimskih DPC-a, Topoizomeraze 1 i 2, pručavan u staničnim modelima, podaci o ovom popravku u organizmima još uvijek su nedostatni. U ovom istraživanju, koristeći model ribe zebrice i ljudske stanične kulture , pokazali smo in vivo da se endogeni popravak TOP1-DPC odvija putem enzima TDP1 i SPRTN, pri čemu ti enzimi djeluju neovisno jedan o drugome. Nadalje, DPC-evi s TOP1 inducirani kemijski, korištenjem kamptotecina ili formaldehida, zahtijevaju međusobno ovisno djelovanje oba enzima kako bi se učinkovito spriječilo nakupljanje oštećenja povezanih s TOP1-DPC-ovima. U ovom radu, pokazali smo kako je zebričin Tdp2 ortolog, Tdp2b, enzim odgovoran za uklanjanje ostataka Top2-DPC-a s DNA. Smanjenje aktivnosti Tdp2, kako u živim organizmima tako i u staničnim modelima, rezultira značajnim fenotipskim promjenama. Ovo istraživanje pruža prve uvide u mehanizme popravka TOP1- i TOP2-DPC-eva in vivo.
Keywords
Keywords (croatian)
Languageenglish
URN:NBNurn:nbn:hr:217:039955
Promotion2023
ProjectNumber: UIP-05-2017
Title: Metode za interpretaciju medicinskih snimki za detaljnu analizu zdravlja srca
Title: Medical Image Interpretation Methods for a Detailed Heart Health Analysis
Leader: Irena Galić
Jurisdiction: Croatia
Funder: HRZZ
Funding stream: Nema
Study programmeTitle: Doctoral study
Study programme type: university
Study level: postgraduate
Academic / professional title: doktor/doktorica znanosti u području prirodnih znanosti (doktor/doktorica znanosti u području prirodnih znanosti)
Type of resourceText
File originBorn digital
Access conditionsEmbargoed access
Embargo expiration date: 2024-11-17
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Created on2023-11-29 12:15:35