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Cilia — or flagella, as they are interchangeably termed — are appendage-like organelles extending from eukaryotic cells. Several recent structural studies on intraflagellar transport (IFT) trains shed light on these fascinating complexes, including their assembly mechanism, stability, cargo recruitment and evolution.
The enzymatic activity of PARP1—which adds chains of (poly-ADP)-ribose (PAR) to proteins—initiates DNA repair by leading to more-accessible chromatin and recruitment of PAR-dependent DNA-repair proteins. New work shows that these PARP1-catalysed functions are redirected by the auxiliary factor HPF1 in cells.
Single-molecule live-cell imaging of the transcription dynamics in budding yeast cells revealed that the remodeling of different nucleosomes in the promoter of a gene regulates various kinetic steps of transcription. The measurements also showed that the TATA-binding protein competes with promoter-associated nucleosomes around the TATA element to activate transcription.
We determined the structure of the Polα–primase complex trapped in a DNA elongation state. Cryo-electron microscopy showed that primase has a role in facilitating the timely termination of primer DNA elongation by Polα by hanging on the primer–template complex.
White adipose tissue secretes the small polypeptide hormone leptin, which controls food intake and satiety. Unlike other metabolic hormones such as insulin and glucagon, leptin does not act on the major metabolic organs liver, muscle, and white adipose tissue, but instead exerts its primary function on the central nervous system.
A cardinal rule of DNA replication is to prevent any possibility of pre-replication complexes re-loading during S phase, risking genotoxic over-replication. But can this rule be broken in emergency situations to preserve genome integrity?
Endogenous retroviruses (ERVs), a type of transposable element (TE), have been incorporated throughout evolution into the human genome. We show that many ERVs regulate placental gene expression, which may have helped fuel the rapid evolution of the placenta and could have implications for pregnancy complications.
The cryo-EM structure of a natural AlkB–AlkG fusion from Fontimonas thermophila reveals the mechanistic basis for its selectivity towards, and functionalization of, alkane terminal C–H groups. AlkB contains an alkane entry tunnel and a diiron active site, and AlkG docks through electrostatic interactions and transfers electrons to the diiron center for catalysis.
The RNA methyltransferase (MTase) METTL1 catalyzes N7-methylguanosine (m7G) modification at position 46 in human transfer RNAs (tRNAs). Its dysregulation drives tumorigenesis in many cancer types. Two papers now reveal the structural basis of this tRNA maturation event.
In this Review, the authors provide a comprehensive overview of recent structural studies of the cGAS–STING complex, discussing pertinent functional and mechanistic implications.
Recent studies offer new insight on the mechanisms of IP6-mediated HIV-1 capsid assembly. The immature Gag lattice enables enrichment of IP6 into virions, aiding capsid maturation. Structures of capsid protein (CA) assemblies reveal motifs serving as switches modulating the conformations of CA pentamers/hexamers and affect co-factor accessibility.
Sperm flagella of highly divergent eukaryotic species share an architectural plan. Despite their ostensible ultrastructural similarities, mammalian sperm flagella beat with an asymmetric waveform, in contrast to the symmetrical beats of other eukaryotic flagella. Structural findings elucidate the molecular basis for this evolutionary divergence.
AlphaFold2 has already changed structural biology, but its true power may lie in how it changes the way we think about cells and organisms. Two studies broadly assess its utility and limitations in providing structural models to shed light in areas such as mutations, protein–protein interactions, and phosphorylation.
Gene transcription initiation is a highly regulated process in which Pol II and general transcription factors assemble into a pre-initiation complex. Structural studies of yeast and human initiation complexes shed light on the role of the first nucleosome flanking gene promoters in controlling the transcription machinery.
Craspase is newly identified type III CRISPR–Cas system with two major components: the nuclease Cas7-11, and the protease TPR-CHAT. Craspases perform a delicate balancing act between nuclease and protease activity to achieve immune tolerance and defense in bacteria, and show promise as highly regulatable genome-editing tools.
New work on DNA polymerase λ highlights its remarkable flexibility. This fits with the generally adaptable nature of the DNA-repair process in which this enzyme is involved—nonhomologous end-joining—which allows this mechanism to handle diverse types of broken DNA ends in order to restore the duplex structure, albeit with a loss of information at the join.
Nuclear actin polymerization helps facilitate chromosome compartment switches that can shift damaged DNA toward a nuclear environment that is favorable for DNA repair. Yet shifting multiple broken DNA strands together can also increase the likelihood of misjoining of the DNA ends and subsequent formation of translocations.
