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

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

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

Izvornik
Chromosome segregation and aneuploidy / - , 2022, 48-48

Skup
EMBO Workshop: Chromosome segregation and aneuploidy

Mjesto i datum
Beč, Austrija, 01.05.2022. - 04.05.2022

Vrsta sudjelovanja
Poster

Vrsta recenzije
Podatak o recenziji nije dostupan

Ključne riječi
Augmin ; Mitosis ; Merotely

Sažetak
The mitotic spindle in human cells consists of microtubules nucleated at the centrosome, at kinetochores and chromosomes, 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, the interkinetochore tension and the mitotic fidelity. Here we show, by using stimulated emission depletion (STED) microscopy and siRNA depletion of HAUS6 or HAUS8 subunits of the augmin complex, that augmin is crucial for the formation of bridging fibers, which laterally link sister kinetochore fibers. Without augmin, the structure of bridging fibers was severely impaired, with 40% of bridging fibers being undetectable in contrast to only 4% in control cells. The number of microtubules within bridging fibers was reduced by 65% and in kinetochore fibers by 30%, suggesting that the bridging fibers, but not kinetochore fibers, are primarily nucleated on the surface of present microtubules. Moreover, bridging fibers had a kinetochore fiber- independent role in the regulation of interkinetochore tension, given that the interkinetochore distance of kinetochore pairs that lack a bridging fiber decreased independently of the thickness of their kinetochore fibers. In HAUS6-depleted cells, the number of lagging kinetochores increased four-fold compared to control cells following Mad2 codepletion. As the lagging kinetochores were typically stretched, which is a signature of merotelic attachment, we propose a role of augmin in the correction of erroneous kinetochore attachments. We also observed misaligned kinetochore pairs that jointly segregated into the same cell and led to aneuploidy, suggesting a role of augmin in chromosome congression. Altogether, we propose a model in which augmin promotes the tension on kinetochores and the mitotic fidelity largely by generating bridging microtubules from the lateral sides of kinetochore microtubules.

Izvorni jezik
Engleski

Znanstvena područja
Biologija

POVEZANOST RADA