Volume 30 Issue 4, April 2023

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?

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.

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.

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 authors perform a computational analysis of mutagenesis at non-B DNA structures formed by repetitive sequences. Having removed confounding factors, they present a landscape of mutagenesis different than previously thought, in which mechanisms such as the formation of abnormal secondary structures, polymerase slippage and occasional takeover by error-prone polymerases play an important role within, but not surrounding, the motifs.

By using nuclear pore complex mimics, the authors demonstrate that the cytoplasm-facing Nup358 provides a dock for the HIV-1 capsid, and the nucleoplasm-facing Nup153 positions the capsid for NPC entry. Nup358 and Nup153 thus create an affinity gradient which regulates capsid penetration, whereas Nup62 constitutes a final NPC gatekeeper against HIV-1 capsid entry.

The authors show that the assembly of the meiotic chromosome axis in worms depends on activation of the master DNA-damage response kinase ATM, which leads to destabilization of the cohesin-unloader WAPL. Similar ATM-dependent WAPL inhibition also occurs in cohesin-rich genomic regions upon DNA-damage induction.

Here, the authors show that replication protein A (RPA) tends to self-assemble into dynamic condensates, in a manner that is stimulated by ssDNA and regulated by RPA2 phosphorylation. RPA condensates are functionally important for telomere clustering and RAD52-dependent telomere maintenance.

Here the authors delineate the chromatin compaction process during human erythropoiesis, observing substantial domain disruption. Heterochromatin is highly compressed and rewired, while transcription competence is a key indicator of the selected domain maintenance.

In this work, the authors show that the DREAM complex suppresses the expression of numerous DNA-repair proteins in somatic cells. Suppression of the DREAM complex, either by altering individual components in Caenorhabditis elegans or chemical inhibition in human cells and progeroid mice, results in increased resistance to various DNA-damage sources during development and aging.

The authors demonstrate that cells that are deficient in H3K9 trimethylation display more compact mitotic chromosomes decorated with aberrantly high H3S10 phosphorylation and H3K27 trimethylation. By quantitative proteomics, they show that H3K9 trimethylation is essential for mitotic bookmarking by Esrrb and thus for the maintenance of epigenetic memory during cell division.

Fluorine nuclear magnetic resonance spectroscopy of the stimulatory heterotrimeric G protein reveals a conformational landscape shaped by interactions with nucleotides, the lipid bilayer and a G-protein-coupled receptor.

Using atomic force microscopy, Pan et al. show that cyclic nucleotide-gated ion channel SthK, which can be differentially activated by cAMP and cGMP, binds both cyclic nucleotides but only cAMP can access a deep-bound state that could be essential for cAMP-dependent channel activation.

Alkane monooxygenase (AlkB) enables diverse microorganisms to hydrolyze alkanes as their sole carbon and energy source. Liu and colleagues reveal how AlkB orients an alkane to its active site and performs a selective terminal C–H bond hydroxylation.

Here the authors investigate the contribution of transposable elements to regulation of gene expression in human trophoblasts. Amongst other examples, they identify an LTR10A element with potential implications for preeclampsia.

Here, the authors show that common fragile sites are unstable under loose activation of the DNA-replication checkpoint. Tight checkpoint activation or CDK1 inhibition stabilizes them by advancing completion of their replication via extra replication-initiation events that are dependent on S-phase availability of proteins involved in pre-RC building.

Tsirigotaki et al. unveil how adipokine Leptin induces trimerization of the Leptin receptor to form a cytokine-receptor assembly critical to body weight regulation, immunity, fertility and cancer.