To build bridges, or to burn them p.481

doi: 10.1038/443481a

Youthful duo snags a swift Nobel for RNA control of genes p.488

doi: 10.1038/443488a

Cosmic ripples net physics prize p.489

doi: 10.1038/443489a

NanotechnologyDownsizing SQUIDs p.517

doi: 10.1038/443517a

GeneticsJunk DNA as an evolutionary force p.521

doi: 10.1038/443521a

Genome-wide genetic analysis of polyploidy in yeast p.541

Polyploidy, increased sets of chromosomes, occurs during development, cellular stress, disease and evolution. Despite its prevalence, little is known about the physiological alterations that accompany polyploidy. We previously described ‘ploidy-specific lethality’, where a gene deletion that is not lethal in haploid or diploid budding yeast causes lethality in triploids or tetraploids. Here we report a genome-wide screen to identify ploidy-specific lethal functions. Only 39 out of 3,740 mutations screened exhibited ploidy-specific lethality. Almost all of these mutations affect genomic stability by impairing homologous recombination, sister chromatid cohesion, or mitotic spindle function. We uncovered defects in wild-type tetraploids predicted by the screen, and identified mechanisms by which tetraploidization affects genomic stability. We show that tetraploids have a high incidence of syntelic/monopolar kinetochore attachments to the spindle pole. We suggest that this defect can be explained by mismatches in the ability to scale the size of the spindle pole body, spindle and kinetochores. Thus, geometric constraints may have profound effects on genome stability; the phenomenon described here may be relevant in a variety of biological contexts, including disease states such as cancer.

doi: 10.1038/nature05178

AB₅ subtilase cytotoxin inactivates the endoplasmic reticulum chaperone BiP p.548

AB₅ toxins are produced by pathogenic bacteria and consist of enzymatic A subunits that corrupt essential eukaryotic cell functions, and pentameric B subunits that mediate uptake into the target cell. AB₅ toxins include the Shiga, cholera and pertussis toxins and a recently discovered fourth family, subtilase cytotoxin, which is produced by certain Shiga toxigenic strains of Escherichia coli. Here we show that the extreme cytotoxicity of this toxin for eukaryotic cells is due to a specific single-site cleavage of the essential endoplasmic reticulum chaperone BiP/GRP78. The A subunit is a subtilase-like serine protease; structural studies revealed an unusually deep active-site cleft, which accounts for its exquisite substrate specificity. A single amino-acid substitution in the BiP target site prevented cleavage, and co-expression of this resistant protein protected transfected cells against the toxin. BiP is a master regulator of endoplasmic reticulum function, and its cleavage by subtilase cytotoxin represents a previously unknown trigger for cell death.

doi: 10.1038/nature05124

Quantum teleportation between light and matter p.557

doi: 10.1038/nature05136

Rapid subtropical North Atlantic salinity oscillations across Dansgaard–Oeschger cycles p.561

doi: 10.1038/nature05121

Lithium isotope evidence for subduction-enriched mantle in the source of mid-ocean-ridge basalts p.565

doi: 10.1038/nature05144

Reassembly of shattered chromosomes in Deinococcus radiodurans p.569

doi: 10.1038/nature05160

Functional epistasis on a common MHC haplotype associated with multiple sclerosis p.574

doi: 10.1038/nature05133

Sodium-dependent uptake of inorganic phosphate by the intracellular malaria parasite p.582

doi: 10.1038/nature05149

Identification of a mammalian mitochondrial porphyrin transporter p.586

doi: 10.1038/nature05125

Molecular architecture and assembly of the DDB1–CUL4A ubiquitin ligase machinery p.590

doi: 10.1038/nature05175

Co-evolution of transcriptional and post-translational cell-cycle regulation p.594

doi: 10.1038/nature05186