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doctoral thesis
DEFINING THE MECHANISM OF POLAR CHROMOSOME CONGRESSION DURING PROMETAPHASE
Zagreb: University of Zagreb, Faculty of Science, 2024. urn:nbn:hr:217:360022
Koprivec, Isabella
University of Zagreb
Faculty of Science
Department of Biology

Institutional repository: Repository of the Faculty of Science

Cite this document

Koprivec, I. (2024). DEFINING THE MECHANISM OF POLAR CHROMOSOME CONGRESSION DURING PROMETAPHASE (Doctoral thesis). Zagreb: University of Zagreb, Faculty of Science. Retrieved from https://urn.nsk.hr/urn:nbn:hr:217:360022

Koprivec, Isabella. "DEFINING THE MECHANISM OF POLAR CHROMOSOME CONGRESSION DURING PROMETAPHASE." Doctoral thesis, University of Zagreb, Faculty of Science, 2024. https://urn.nsk.hr/urn:nbn:hr:217:360022

Koprivec, Isabella. "DEFINING THE MECHANISM OF POLAR CHROMOSOME CONGRESSION DURING PROMETAPHASE." Doctoral thesis, University of Zagreb, Faculty of Science, 2024. https://urn.nsk.hr/urn:nbn:hr:217:360022

Koprivec, I. (2024). 'DEFINING THE MECHANISM OF POLAR CHROMOSOME CONGRESSION DURING PROMETAPHASE', Doctoral thesis, University of Zagreb, Faculty of Science, accessed 28 December 2024, https://urn.nsk.hr/urn:nbn:hr:217:360022

Koprivec I. DEFINING THE MECHANISM OF POLAR CHROMOSOME CONGRESSION DURING PROMETAPHASE [Doctoral thesis]. Zagreb: University of Zagreb, Faculty of Science; 2024 [cited 2024 December 28] Available at: https://urn.nsk.hr/urn:nbn:hr:217:360022

I. Koprivec, "DEFINING THE MECHANISM OF POLAR CHROMOSOME CONGRESSION DURING PROMETAPHASE", Doctoral thesis, University of Zagreb, Faculty of Science, Zagreb, 2024. Available at: https://urn.nsk.hr/urn:nbn:hr:217:360022

Metadata
TitleDEFINING THE MECHANISM OF POLAR CHROMOSOME CONGRESSION DURING PROMETAPHASE
Title (english)ODREĐIVANJE MEHANIZMA KONGRESIJE POLARNIH KROMOSOMA TIJEKOM PROMETAFAZE
AuthorIsabella Koprivec
MentorIva Marija Tolić (mentor)
Committee memberPetar Ozretić (predsjednik povjerenstva)
Committee memberBiljana Balen (član povjerenstva)
GranterUniversity of Zagreb
Faculty of Science
(Department of Biology)
Zagreb
Defense date and country2024-10-09, Croatia
Scientific / art field,
discipline and subdiscipline		NATURAL SCIENCES
Biology
Universal decimal classification
(UDC)		576 - Cellular and subcellular biology. Cytology
Abstract
Chromosomes that first attach to the mitotic spindle behind the spindle pole (i.e., polar) are delayed in alignment and prone to segregation errors. Nevertheless, their congression mechanism remains elusive. Using a unique combination of advanced microscopy techniques, I showed that polar chromosomes rely on the pivoting of chromosome-attached astral microtubules around the centrosome to cross the pole. By altering the KIF11/Eg5 activity to reverse, restore, or block spindle elongation, I demonstrated that spindle elongation directs pivoting. I also revealed impaired spindle elongation as a major cause of unalignment for polar chromosomes in hTERT-immortalized retinal pigment epithelial RPE1 cells after TTK/MPS1 kinase inhibition and in the high-grade serous ovarian carcinoma OVSAHO cells. Increasing spindle elongation efficiency by depleting KIF4A rescued unaligned chromosomes in OVSAHO cells, supporting the conclusion that polar chromosomes depend on spindle elongation-driven pivoting to cross the pole and avoid missegregation.
Abstract (english)
Polarni kromosomi stvaraju prvu vezu s diobenim vretenom iza pola te pokazuju sklonost kasnom poravnanju i stvaranju kromosomskih grešaka. Unatoč tome, njihov mehanizam kongresije još uvijek je nerazjašnjen. Koristeći jedinstvenu kombinaciju naprednih mikroskopijskih metoda, predlažem hipotezu da polarni kromosomi prelaze pol zahvaljujući pivotiranju astralnih mikrotubula vezanih za kromosome oko centrosoma. Promjenom aktivnosti KIF11/Eg5 kako bi se narušilo, popravilo ili zaustavilo produljenje diobenog vretena, pokazala sam da produljenje vretena usmjerava pivotiranje. Također, pokazala sam da narušeno produljenje vretena uzrokuje pojavu neporavnanih polarnih kromosoma u hTERT-imortaliziranim retinalnim pigmentnim epitelnim stanicama RPE1 s inhibiranom kinazom TTK/MPS1, kao i u stanicama seroznog raka jajnika visokog stupnja malignosti OVSAHO. Povećanje učinkovitosti produljenja diobenog vretena deplecijom KIF4A spasilo je neporavnane kromosome u stanicama OVSAHO, što podržava hipotezu da polarni kromosomi ovise o pivotiranju vođenom produljenjem vretena kako bi uspješno prešli pol i izbjegli stvaranje grešaka tijekom diobe.
Keywords
Keywords (english)
Languageenglish
URN:NBNurn:nbn:hr:217:360022
Promotion2024
ProjectNumber: PZS-2019-02-7653
Title: Mehanizmi nastajanja snopova mikrotubula potrebni za sazrijevanje diobenog vretena
Title: Mechanisms of microtubule bundle formation required for spindle maturation
Acronym: SpindleForm
Leader: Iva Marija Tolić
Jurisdiction: Croatia
Funder: Hrvatska zaklada za znanost
Funding stream: Programme Research Cooperability
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 conditionsOpen access
Terms of useLicence In copyright icon
Created on2024-12-02 11:58:36