MECHANISM OF CHROMOSOME ALIGNMENT BY MICROTUBULE OVERLAPDEPENDENT FORCES AND ITS RELEVANCE FOR CHROMOSOME SEGREGATION ERRORS

doctoral thesis

• Title (croatian): MEHANIZAM PORAVNANJA KROMOSOMA SILAMA KOJE OVISE O PREKLAPANJU MIKROTUBULA I NJEGOV UTJECAJ NA POGREŠKE U RAZDVAJANJU KROMOSOMA
• Author: Patrik Risteski
• Mentor: Iva Marija Tolić (mentor)
• Committee member: Vedrana Filić Mileta (predsjednik povjerenstva)
• Committee member: Biljana Balen (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2022-10-11, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology
• Universal decimal classification (UDC): 576 - Cellular and subcellular biology. Cytology

Abstract

Chromosome alignment is a hallmark of mitosis and alignment defects, which persist in
anaphase, lead to direct aneuploidy. Alignment at the spindle equator depends on pulling forces
exerted at kinetochore fiber tips together with polar ejection forces. However, kinetochore
fibers are also subjected to forces that drive their poleward flux. Here I introduce a microtubule
flux-driven centering mechanism that relies on flux generated by forces within the overlaps of
bridging and kinetochore fibers. This centering mechanism works so that the longer kinetochore
fiber fluxes faster than the shorter one, moving the kinetochores towards the center.
Kinetochores are better centered when overlaps are shorter and the kinetochore fiber flux is
markedly slower than the bridging fiber flux. I identified Kif18A and Kif4A proteins as overlap
and flux regulators and NuMA protein as a fiber coupler. Thus, I propose that length-dependent
sliding forces exerted by the bridging fiber onto kinetochore fibers support chromosome
alignment.

Abstract (croatian)

Poravnanje kromosoma je jedno od obilježja mitoze i problemi u poravnavanju, koji opstaju u
anafazi, vode izravnoj aneuploidiji. Poravnanje na ekvatoru vretena ovisi o silama vučenja koje
djeluju na vrhove kinetohornih vlakana zajedno sa silama izbacivanja s pola. Međutim,
kinetohorna vlakna također su podvrgnuta silama koje pokreću njihov tok prema polu. U ovom
radu predstavljam mehanizam za centriranje vođen tokom mikrotubula koji se oslanja na tok
generiran silama unutar preklopa između premošćujućih i kinetohornih vlakana. Ovaj
mehanizam centriranja radi tako da duže kinetohorno vlakno teče brže od kraćeg, što pomiče
kinetohore prema centru. Kinetohore su bolje centrirane kada su preklapanja kraća i tok
kinetohornih vlakana izrazito sporiji od toka premošćujućih vlakana. Identificirao sam proteine
Kif18A i Kif4A kao regulatore preklapanja i toka mikrotubula i protein NuMA kao spojnicu
vlakana. Stoga predlažem da sile klizanja koje su ovisne o duljini, a koje premošćujuće vlakno
prenosi na kinetohorna vlakna, podržavaju poravnanje kromosoma.

• Keywords: mitotic spindle; chromosome alignment; kinetochores; microtubule poleward flux; speckle microscopy; chromosome segregation errors
• Keywords (croatian): diobeno vreteno; poravnanje kromosoma; kinetohore; tok mikrotubula prema polu; speckle mikroskopija; pogreške u podjeli kromosoma
• Language: english
• URN:NBN: urn:nbn:hr:217:637095
• Promotion: 2022
• Study programme: Title: Biology; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje prirodnih znanosti, polje biologija (doktor/doktorica znanosti, područje prirodnih znanosti, polje biologija)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2022-11-17 11:51:28