Volume 27 Issue 2, February 2020

Technological advances have led to new insights into genome-wide arrangements of nucleosomes along the DNA and the folding of the chromosome fiber in nuclear space, revealing unexpected diversity.

Cryo-EM structures of nick forming complexes of the mouse RAG recombinase with DNA substrates demonstrate how the RAG active site is reconfigured for two consecutive DNA cleavage reactions.

Structural elucidation of the RAG strand transfer complex reveals how the recombinase efficiently catalyzes both forward and reverse integration reactions to prevent RAG-mediated transposition events.

Crystal structures of human BRAF kinase domain with MEK and an ATP analog or with 14-3-3 reveal how ATP exerts a negative regulatory effect on the kinase and how this effect is relieved by dimeric 14-3-3.

The cryo-EM structure of Bcs1, an AAA-ATPase of the inner mitochondrial membrane, reveals two large aqueous vestibules separated by a seal-forming middle domain, an architecture that suggests an airlock-like translocation mechanism for its folded substrate.

Cryo-EM structures of the calcium homeostasis modulator channels chicken CALHM1 and human CALHM2 reveal that they function as octa- and undecamers, respectively. Molecular dynamics simulations suggest that a lipid bilayer can form within the CALHM2 pore.

Solid-state NMR structures of the influenza B M2 (BM2) proton channel transmembrane domain in a phospholipid environment reveal open and closed conformations and indicate that side chain dynamics are essential for proton shuttling by BM2.

Knockout screens to assess the effect of LINE-1 expression on cell growth show that TP53-deficient cells require replication-stress signaling and replication-fork restart factors to suppress LINE-1 toxicity, and that LINE-1 expression activates the Fanconi anemia pathway, suggesting that retrotransposition conflicts with DNA replication.

Whole-genome siRNA screens to identify regulators of human LINE-1 retrotransposition reveal that BRCA1 and Fanconi anemia DNA repair factors inhibit retrotransposition at stalled replication fork targets created and exploited by L1.

Mutations in cysteine string protein-α (CSPα) cause its aggregation and adult-onset neuronal ceroid lipofuscinosis. Abnormal binding of Fe–S clusters to CSPα mutants is now implicated in driving aggregation, which can be reversed in neurons by clinically approved iron chelators.

Structures of mouse Bcs, a mitochondrial membrane-bound AAA protein, in two different conformations reveal a potential mechanism of translocating folded proteins across a membrane and allow mapping of human disease-associated mutations.

NEDD8-ubiquitin substrate profiling (sNUSP) identifies neddylation sites in many non-cullin proteins. Among the candidates, neddylation of cofilin regulates actin dynamics and neurite growth and outgrowth in developing neurons.