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New structures of SH3 domains complexed with proline-rich peptides show that the ligands can bind in two opposite orientations; this feature has not been seen before in protein/protein recognition.

Measuring air temperature is far from a trivial task, as Andrea Merlone, Graziano Coppa and Chiara Musacchio explain.

Metrology and meteorology: just two letters separating two similar and frequently confused words. Andrea Merlone, Chiara Musacchio and Walter Bich tell us about these different disciplines and ways in which they collaborate.

The spindle assembly checkpoint protects cells from chromosome missegregation. Here, the authors use sophisticated biochemical reconstitutions to address how kinetochores, the microtubule-binding structures of chromosomes, regulate this checkpoint.

To celebrate almost 50 years from the discovery of tubulin, six eminent researchers reflect on how the field of microtubule research has advanced over the past five decades, discuss impacts on clinical translation, and provide their thoughts on what key questions need to be addressed in the near future.

Biochemical reconstitution of a synthetic human kinetochore with 21 protein subunits and centromeric nucleosomal DNA unveils fundamental principles of kinetochore organization and function.

The near-complete in vitro reconstitution of the mitotic spindle assembly checkpoint reveals how the assembly of its effector, the mitotic checkpoint complex, is catalysed.

Mitotic exit follows shortly after microtubule attachment of the last unattached kinetochore. Two new studies illustrate the molecular basis of this dependency.

The spindle-assembly checkpoint is a safety device that monitors the attachment of spindle microtubules to kinetochores and ensures the fidelity of chromosome segregation in mitosis. Molecular studies are finally starting to reveal the mechanisms of checkpoint activation and inactivation.

The CENP-A chaperone HJURP associates with Mis18α, Mis18β, and M18BP1 to target centromeres and deposit new CENP-A. Here the authors provide evidence that two repeats in human HJURP previously proposed to be functionally distinct are interchangeable and bind concomitantly to the 4:2:2 Mis18α:Mis18β:M18BP1 complex without dissociating it.

SKAP and Astrin form a heterodimer that localizes to spindle microtubules and to mature microtubule-kinetochore attachments during mitosis. Here, the authors identify molecular requirements for the inter-subunit interaction of SKAP and Astrin and kinetochore recruitment.

During cell division, kinetochores anchor chromosomes to spindle microtubules. Here, the authors report a comprehensive structure–function analysis of the kinetochore’s main microtubule receptor, the KMN network, shedding new light on its organization.

The concluding statement of Watson and Crick’s historic paper on the structure of DNA¹ enshrines a key tenet of molecular mechanistic cell biology: “… the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material”. Function — heredity in this case — is embedded in the redundant sequence information of the two strands of DNA. Although not always expressed as blatantly, the intimate dependence of cellular function on the mechanical level of macromolecules is inspirational. The devil is in the structural detail, and the painstaking quest for the correct details and their returns in the form of reliable knowledge knows no shortcuts.

Lim et al. reconstitute in vitro the transition between metaphase and anaphase-like spindle midzone architectures and dissect the role of PRC1 phosphorylation by PLK and CDK1 in reorganizing the central spindle during mitosis.

The formation of the mitotic checkpoint complex requires an intricate spatial coordination amongst the proteins Bub1, Mad1, Cdc20, and Mad2. Chen et al show that a structural flexibility in Mad1 plays an essential role in achieving this coordination.

How p97 processes diverse clients has remained controversial. van den Boom, Kueck and colleagues now demonstrate that p97 recognizes an internal segment of the PP1 partner I3 and then threads an I3 peptide loop through the channel in p97 to strip I3 off PP1.

LGN and NuMA link epithelial polarity sites with astral microtubules and associate with dynein, but the architecture of such cortical force-generating complexes is unknown. Here, the authors report the crystal structure of NuMA:LGN hetero-hexamers, and unveil their role in promoting the assembly of active cortical dynein/dynactin motors.

Sacristan et al. show that the dynein adaptor Spindly facilitates oligomerisation of the RZZ complex to expand the kinetochore, after which Spindly-associated dynein compacts the kinetochore to allow for faithful chromosome segregation.

The Ndc80 complex is a key component of kinetochore that mediates direct interaction with spindle microtubules. These authors present a cryo-electron microscopy reconstruction of Ndc80 bound to microtubules. They find that Ndc80 uses a novel microtubule recognition mode coupling tubulin binding to self-oligomerization of the complex, and present a mechanistic model for the formation of high-affinity kinetochore–microtubule attachments during cell division.

The adhesion molecule Afadin acts as a scaffold coordinating the cortical assembly of the cellular machinery that orients the mitotic spindle and drives planar cell division.

Whether cohesion-independent forces hold chromosomes together in metaphase is a debated issue. Artificial cleavage of cohesin is sufficient to induce chromosome disjunction in Drosophila syncytical embryos but cdk1 inactivation is required for normal subsequent chromosome separation.

Aneuploidy, which results from chromosome mis-segregation, is a hallmark of cancer, but it can also inhibit tumorigenesis. Recent studies on the short- and long-term consequences of aneuploidy, which are caused by gene-specific effects and a stereotypic aneuploidy stress response, provide insights into this contradictory role in tumorigenesis.