Spindle assembly at a BRISC pace

Yan et al. describe how a deubiquitinating enzyme complex regulates the mitotic spindle assembly factor NuMA. BRCC36 is a de-ubiquitinating enzyme that preferentially cleaves lysine 63–linked poly-ubiquitin 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, ubiq-uitinated NuMA showed an increased association with both im-portin-␤ 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-defi cient cells progress through mitosis, despite their disorganized spindles, he is particularly interested in whether the deubiquitinase can regulate the spindle assembly checkpoint. Nyathi and Pool describe how a chaperone complex helps ensure nascent polypeptides are correctly processed as they emerge from ribosomes. Newly synthesized proteins must be quickly modified, folded, and targeted to their correct destination within the cell. Many of the factors responsible for these processing steps bind to the same " universal adaptor site " (UAS) on ribosomes, allowing them to target nascent polypeptides as soon as they emerge. How the binding of these factors is coordinated so that each polypep-tide gets processed correctly remains unclear. Nyathi and Pool found that Map1, a budding yeast enzyme that cleaves the N-terminal methionine off of most cytosolic proteins , also binds to the UAS, adjacent to the ␣ subunit of a ribo-some-associated chaperone complex called NAC. Overexpressing Map1 displaced the signal recognition particle (SRP), which guides nascent secretory and membrane proteins to the ER, suggesting that Map1 and SRP compete for a binding site within the UAS. Overexpressing SRP, however, failed to displace Map1 from ribosomes unless the researchers removed NAC—particularly its …