THE ROLE OF MITOTIC KINESINS AND CROSSLINKERS NUMA AND PRC1 IN THE MICROTUBULE POLEWARD FLUX REGULATION DURING PROMETAPHASE

doctoral thesis

• Title (croatian): ULOGA MITOTSKIH KINEZINA I VEZNIH PROTEINA NUMA I PRC1 U REGULACIJI TOKA MIKROTUBULA U PROMETAFAZI
• Author: Jelena Martinčić
• Mentor: Iva Marija Tolić (mentor)
• Committee member: Maja Matulić (predsjednik povjerenstva)
• Committee member: Marin Barišić (član povjerenstva)
• Committee member: Andreja Ambriović Ristov (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2023-12-11, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology
• Universal decimal classification (UDC): 577 - Biochemistry. Molecular biology. Biophysics

Abstract

Microtubule poleward flux is a fascinating phenomenon that occurs throughout mitosis,
including prometaphase. Studying the involvement of different proteins in prometaphase flux
regulation is challenging because of high dynamics of microtubule and chromosome
movements in this phase. Here I show that the prometaphase spindle consists of k-fibers and
bridging fibers, and their poleward flux velocities are similar as in metaphase. By using
tubulin photoactivation and speckle microscopy experiments I defined the role of mitotic
kinesins and passive crosslinkers in the flux regulation. CENP-E and HSET are generating
flux at the antiparallel fibers and this force is transmitted to the k-fibers via HSET and
NuMA. The congressing kinetochores are asymmetrically bioriented with more microtubules
on the side of the closer pole, and interkinetochore distance close to the metaphase values. I
demonstrated that kinetochores congress on long antiparallel overlaps, and the flux is
generating forces that help the congression.

Abstract (english)

Tok mikrotubula prema polu je fascinantan fenomen koji se događa tijekom mitoze,
uključujući i prometafazu. Proučavanje uloge različitih proteina u regulaciji toka mikrotubula
je izazovno zbog velike dinamike u kretnji mikrotubula i kinetohora u toj fazi mitoze. Ovdje
sam pokazala da se prometafazno vreteno sastoji od kinetohornih i premošćujućih vlakana
kojima su brzine toka mikrotubula slične kao u metafazi. Koristeći metode fotoaktivacije i
“speckle” mikroskopije definirala sam ulogu mitotskih kinezina i pasivnih veznika u
regulaciji toka mikrotubula. CENP-E i HSET pokreću tok mikrotubula u antiparalelnim
vlaknima, a ta sila se prenosi na k-vlakna pomoću proteina HSET i NuMA. Kinetohore su
tijekom kongresije asimetrično biorijentirane s više mikrotubula na strani prema bližem polu,
a interkinetohornom udaljenošću blizu vrijednosti u metafazi. Pokazala sam da se kongresija
događa na dugim antiparalelnim snopovima, a tok mikrotubula proizvodi sile koje pomažu u
kongresiji.

• Keywords: mitosis; prometaphase; mitotic spindle; microtubule poleward flux; kinesins; congression
• Keywords (english): mitoza; prometafaza; mitotsko vreteno; tok mikrotubula prema polu; kinezini; kongresija
• Language: english
• URN:NBN: urn:nbn:hr:217:456407
• Promotion: 2024
• Project: Number: Grant agreement ID: 855158; Title: Molecular origins of aneuploidies in healthy and diseased human tissues (Aneuploidy); Jurisdiction: eu; Funder: EXCELLENT SCIENCE - European Research Council (ERC)
• 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: 2024-01-11 12:06:15