Yan et al. describe how a deubiquitinating enzyme complex regulates the mitotic spindle assembly factor NuMA.

BRCC36 is a deubiquitinating enzyme that preferentially cleaves lysine 63–linked polyubiquitin chains. As part of the Rap80 complex, BRCC36 regulates the repair of DNA double-strand breaks, but the enzyme can also assemble into a distinct complex, known as BRISC.

Yan et al. found that knocking down BRCC36, or a subunit unique to the BRISC complex called ABRO1, caused mitotic cells to assemble multipolar spindles that frequently aligned and segregated chromosomes incorrectly. These defects could not be rescued by a catalytically inactive version of BRCC36. In wild-type mitotic cells, BRISC accumulated at the spindle poles, bound to the minus ends of stable, kinetochore-attached microtubules. Early in mitosis, BRISC also localized near the kinetochores themselves, where it promoted the chromosome-dependent nucleation of spindle microtubules.

Yan et al. discovered that BRISC binds and deubiquitinates the spindle assembly factor NuMA, which captures and focuses microtubules at spindle poles. In the absence of BRISC, ubiquitinated NuMA showed an increased association with both importin-β and dynein, which regulate the protein’s function.

BRISC therefore promotes bipolar spindle assembly by deubiquitinating NuMA. Senior author Genze Shao says that BRISC may have other mitotic substrates as well. Because some BRISC-deficient cells progress through mitosis, despite their disorganized spindles, he is particularly interested in whether the deubiquitinase can regulate the spindle assembly checkpoint.

, et al
J. Cell Biol.

Author notes

Text by Ben Short