THE ROLES OF AUGMIN AND SPINDLE ACTIN IN CHROMOSOME CONGRESSION, SPINDLE ARCHITECTURE AND MITOTIC FIDELITY

doctoral thesis

• Title (croatian): ULOGE AUGMINA I AKTINA UNUTAR DIOBENOG VRETENA U KONGRESIJI KROMOSOMA, ARHITEKTURI VRETENA I VJERNOSTI MITOZE
• Author: Valentina Štimac
• Mentor: Iva Marija Tolić (mentor)
• Committee member: Andreja Ambriović Ristov (predsjednik povjerenstva)
• Committee member: Maja Matulić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2024-10-23, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology
• Universal decimal classification (UDC): 576 - Cellular and subcellular biology. Cytology

Abstract

The human mitotic spindle is made of microtubules nucleated at centrosomes, at kinetochores, and from pre-existing microtubules by the augmin complex. Recently, spindle actin also emerged as a possible player in spindle assembly. However, it is unknown how augmin-mediated nucleation affects distinct microtubule classes, what the spatial distribution of spindle actin and microtubules is, and, finally, what the roles of these two proteins are in spindle architecture and mitotic progression. Here, by using superresolution microscopy and cutting edge live-cell imaging, I found that augmin promotes mitotic fidelity by generating assemblies consisting of bridging and kinetochore fibers that align sister kinetochores to face opposite poles, thereby preventing erroneous attachments. Furthermore, I showed that spindle actin, by forming fine filaments in the polar region and along spindle microtubules, promotes spindle pole focusing and bipolar cell division.

Abstract (croatian)

Mikrotubuli diobenog vretena se u ljudskim stanicama nukleiraju na centrosomu, kinetohorama te na površini već postojećih mikrotubula pomoću augminskog kompleksa. Nedavno je predloženo da i aktin unutar diobenog vretena ima ulogu u njegovom sastavljanju. Međutim, još uvijek nije poznato na koji način nukleacija pomoću augmina utječe na različite klase mikrotubula, koja je prostorna raspodjela aktina i mikrotubula unutar vretena te koja je uloga ova dva proteina u arhitekturi vretena i progresiji mitoze. Koristeći superrezolucijsku mikroskopiju te najnoviju tehnologiju snimanja živih stanica pokazala sam da augmin ima ulogu u pravilnoj podjeli kromosoma. Augmin stvara sklopove mikrotubula koji se sastoje od premošćujućih i kinetohornih vlakana što poravnava sestrinske kinetohore na način da su okrenute prema suprotnim polovima, te tako sprječava pogrešna vezanja s mikrotubulima. Nadalje, pokazala sam da aktin unutar vretena promiče fokusiranje polova vretena te bipolarnu mitozu tako što formira filamente u polarnoj regiji te uzduž mikrotubula.

• Keywords: mitotic spindle; augmin; spindle actin; microtubule nucleation; chromosome congression; chromosome segregation
• Keywords (croatian): diobeno vreteno; augmin; aktin unutar vretena; nukleacija mikrotubula; kongresija kromosoma; podjela kromosoma
• Language: english
• URN:NBN: urn:nbn:hr:217:130520
• Promotion: 2024
• Project: Number: 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 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: 2024-12-02 18:11:40