PT  - JOURNAL ARTICLE
AU  - Andrea Serra-Marques
AU  - Ronja Houtekamer
AU  - Dorine Hintzen
AU  - John T. Canty
AU  - Ahmet Yildiz
AU  - Sophie Dumont
TI  - The mitotic protein NuMA plays a spindle-independent role in nuclear formation and mechanics
AID  - 10.1101/2020.05.02.070680
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.05.02.070680
4099  - http://biorxiv.org/content/early/2020/05/03/2020.05.02.070680.short
4100  - http://biorxiv.org/content/early/2020/05/03/2020.05.02.070680.full
AB  - Eukaryotic cells typically form a single, round nucleus after mitosis, and failures to do so can compromise genomic integrity. How mammalian cells form such a nucleus remains incompletely understood. NuMA is a spindle protein whose disruption results in nuclear fragmentation. What role NuMA plays in nuclear integrity, or whether its perceived role stems from its spindle function, is unclear. Here, we use live imaging to demonstrate that NuMA plays a spindle-independent role in forming a single, round nucleus. NuMA keeps the decondensing chromosome mass compact at mitotic exit, and promotes a mechanically robust nucleus. NuMA’s C-terminus binds DNA in vitro and chromosomes in interphase, while its coiled-coil acts as a regulatory and structural hub: it prevents NuMA from binding chromosomes at mitosis, regulates its nuclear mobility and is essential for nuclear formation. Thus, NuMA plays a long-range structural role in building and maintaining an intact nucleus, as it does for the spindle, playing a protective role over the cell cycle.Competing Interest StatementThe authors have declared no competing interest.