Proučavanje uloge toka mikrotubula u centriranju kromosoma u diobenom vretenu tijekom mitoze

doctoral thesis

• Title (english): Studying the role of microtubule flux in chromosome centering on the mitotic spindle
• Author: Domagoj Božan
• Mentor: Nenad Pavin (mentor)
• Committee member: Matko Glunčić (predsjednik povjerenstva)
• Committee member: Nenad Pavin (član povjerenstva)
• Committee member: Iva Marija Tolić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Physics); Zagreb
• Defense date and country: 2024-11-29, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Physics
• Universal decimal classification (UDC): 53 - Physics

Abstract

Mitoza je proces podjele stanice majke u dvije identične stanice kćeri te se tradicionalno dijeli na pet faza: profazu, prometafazu, metafazu, anafazu i telofazu. Tijekom prometafaze, kromosomi se gibaju unutar stanice u procesu zvanom kongresija sve dok ne postignu pravilnu bipolarnu orijentaciju na metafaznoj ravnini. Nakon toga stanica ulazi u metafazu, gdje se kromosomi centriraju na ekvatoru diobenog vretena. Procesi koji se odvijaju tijekom prometafaze i metafaze utječu na ispravno poravnanje kromosoma i stoga su od velikog značaja za ispravno daljnje provođenje mitoze. Diobeno se vreteno sastoji od dva pola na kojima se nukleiraju mikrotubuli. Interakcije mikrotubula i kinetohora te sile koje generiraju proteini ono su što vodi gibanje kromosoma. Kinetohorni mikrotubuli pod utjecajem su sila koje vode njihov tok usmjeren prema polu (eng. poleward flux). U ovom je radu razvijen model centriranja kromosoma u diobenom vretenu tijekom mitoze pomoću toka mikrotubula usmjerenog prema polu, koji se primjenjuje na prometafazu i metafazu. Model se sastoji od jednog para sestrinskih kinetohora izmaknutih iz središta diobenog vretena na koje se vežu kinetohorni mikrotubuli koji stvaraju paralelne i antiparalelne preklope s premosnim mikrotubulima. Unutar tih preklopa vežu se proteini koji generiraju sile ovisne o duljini mikrotubula koje vode njihov tok. Ravnoteža sila u modelu utječe na brzine toka kinetohornih mikrotubula i brzine kinetohora. Rezultati modela za metafazu pokazuju da se kinetohore približavaju središtu diobenog vretena unutar nekoliko minuta. Model također daje ključno i jedinstveno predviđanje da su za kinetohore izmaknute iz središta duži kinetohorni mikrotubuli podvrgnuti bržem toku od kraćih. Model za prometafazu uvodi i razliku u broju kinetohornih mikrotubula na sestrinskim kinetohorama, gdje se kraći mikrotubuli nalaze u većem broju. Rezultati ovog modela pokazuju da će sile na manjem broju duljih kinetohornih mikrotubula nadjačati sile na većem broju kraćih i time uzrokovati gibanje kromosoma prema metafaznoj ravnini, odnosno kongresiju.

Abstract (english)

Mitosis is the process in which one mother cell is divided into two identical daughter cells and it is traditionally divided into five phases: prophase, prometaphase, metaphase, anaphase and telophase. During prometaphase, chromosomes move within the cell in a process named congression until they reach proper bipolar orientation on the metaphase plate. After that the cell enters metaphase, where the chromosomes center on the mitotic spindle equator. Processes occurring during prometaphase and metaphase affect the proper alignment of chromosomes and are therefore of great importance for proper completion of mitosis. The mitotic spindle consists of two poles on which microtubules are nucleated. The interactions between microtubules and kinetochores, as well as forces generated by proteins are what drives chromosome movement. Kinetochore microtubules are subject to forces driving their poleward flux. In this paper a model for chromosome centering in the mitotic spindle through microtubule poleward flux has been developed and applied to prometaphase and metaphase. The model consists of one pair of sister kinetochores placed away from the mitotic spindle center onto which kinetochore microtubules are attached, forming parallel and antiparallel overlaps with bridging microtubules. Within those overlaps proteins accumulate and generate length-dependent forces driving microtubule poleward flux. The balance of forces in the model affects kinetochore microtubule flux and kinetochore velocities. The results of the metaphase model show that kinetochore approach the mitotic spindle center in several minutes. The model also present a key unique prediction that for kinetochore placed away from the center longer kinetochore microtubules have greater poleward flux than shorter ones. The prometaphase model introduces a difference in number of kinetochore microtubules on the sister kinetochores, where the number of shorter microtubules is greater. The results of this model show that the forces on lesser number of longer kinetochore microtubules will overpower the forces on greater number of shorter ones and thus cause chromosome movement towards the metaphase plate, or in other words, congression.

• Keywords: mitoza; prometafaza; metafaza; kongresija; centriranje; kromosomi; mikrotubuli; tok mikrotubula prema polu; motorni proteini
• Keywords (english): mitosis; prometaphase; metaphase; congression; centering; chromosomes; microtubules; microtubule poleward flux; motor proteins
• Language: croatian
• URN:NBN: urn:nbn:hr:217:862890
• Promotion: 2025
• Project: Number: 855158; Title: Molekularno podrijetlo aneuploidija u zdravim i bolesnim ljudskim tkivima; Title: Molecular origins of aneuploidies in healthy and diseased human tissues; Acronym: ANEUPLOIDY; Leader: Iva Marija Tolić; Jurisdiction: eu; Funder: Europska unija
• Study programme: Title: 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 resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2025-01-21 12:27:43