Naslov
Augmin regulates kinetochore tension and mitotic fidelity by nucleating bridging fibers

Autori
Štimac, Valentina ; Koprivec, Isabella ; Manenica, Martina ; Simunić, Juraj ; Tolić, Iva M.

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Skup
Cell Bio Virtual 2021 - An Online ASCB|EMBO Meeting

Mjesto i datum
San Diego (CA), Sjedinjene Američke Države, 01.12.2021. - 10.12.2021

Vrsta sudjelovanja
Predavanje

Vrsta recenzije
Podatak o recenziji nije dostupan

Ključne riječi
Augmin ; Microtubules ; Nucleation

Sažetak
The mitotic spindle in human cells consists of microtubules mainly nucleated at the centrosome and on the lateral surface of existing microtubules by the augmin complex. However, it is unknown how the augmin-mediated nucleation affects functionally distinct microtubule bundles and consequently the forces within the spindle. Here we show, by using stimulated emission depletion (STED) microscopy and siRNA depletion of HAUS6 or HAUS8 subunits of the augmin complex that augmin plays a crucial role in the proper formation of bridging fibers, which laterally link sister kinetochore fibers. After depletion, the structure of bridging fibers was severely impaired with the majority of bridging fibers either missing or improperly attaching to sister kinetochore fibers. Confocal microscopy revealed that the augmin depletion reduced the number of microtubules within bridging fibers by around 80% and in kinetochore fibers by 40%, suggesting that the bridging microtubules are mainly nucleated at the surface of present microtubules. Moreover, the interkinetochore distance decreased preferentially for kinetochores that lack a bridging fiber, independently of the thickness of their k-fibers, implying that augmin affects forces on kinetochores largely via bridging fibers. Without augmin, the decreased number of bridging fibers was accompanied by their spatial rearrangement within the spindle and slower poleward flux of k- fibers. Augmin depletion also resulted in chromosome segregation errors, nucleus fragmentation and the appearance of micronuclei. We propose a model in which augmin promotes tension on kinetochores and mitotic fidelity by generating bridging microtubules from the lateral sides of kinetochore microtubules.

Izvorni jezik
Engleski

POVEZANOST RADA