Detection of "hidden" mitotic crossovers by long-read DNA sequencing.

September 26, 2026| Source: Proceedings of the National Academy of Sciences of the United States of America

Mitotic crossovers in diploid organisms are usually detected by looking for loss of heterozygosity (LOH) for a marker. Assuming the crossover occurs between two duplicated chromatids, a single reciprocal crossover will result in two recombinant chromatids and two nonrecombinant chromatids. LOH will only be observed when a recombinant chromatid cosegregates with a nonrecombinant chromatid. Cells containing both recombinant chromosomes will not result in LOH. Below, we use long-range DNA sequencing to detect crossovers that do not produce LOH, the "hidden" crossovers. In wild-type diploids of Saccharomyces cerevisiae , these crossovers occur at a rate of about 4 × 10 -4 /cell division. Long-range sequencing also allows the detection of gene conversions associated with crossovers in samples derived from a single cell. Last, we showed that hydrogen peroxide treatment of G1-arrested cells not only induces frequent recombination, but also a high proportion of two-strand mutation events in which both DNA strands are mutated at the same position prior to replication.

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PLASTID ENVELOPE ION CHANNELS (PEC1/2) link Ca 2+ and jasmonic acid signaling in plant cells.

Plants constantly encounter adverse environmental interactions. One organelle is particularly specialized in stress signaling and phytohormone synthesis: the plastid. Calcium (Ca 2+ ), a key second messenger, is known to intersect with cellular phytohormone signaling networks. While cytosolic Ca 2+ dynamics have been studied extensively, the physiological relevance of stromal Ca 2+ transients and the identity of channels mediating rapid Ca 2+ flux into plastids remain largely unexplored. In this

Health & MedicineSeptember 26, 2026

Amino acid homeostasis by CORVET/HOPS: A metabolic and stress resilience checkpoint for T cells.

Amino acid sufficiency is critical for T cell metabolic reprogramming, yet how T cells maintain amino acid homeostasis remains poorly defined. Here, we identify the CORVET and HOPS (CORVET/HOPS) tethering complexes as essential upstream regulators. In activated T cells, they sustain intracellular amino acid levels by promoting macropinocytosis to acquire extracellular nutrients. This function enables dual signaling outcomes: suppression of the integrated stress response (ISR) and activation of m

Health & MedicineSeptember 25, 2026

Bright monomeric fluorescent protein elite-niRFP704 for two-channel near-infrared STED nanoscopy.

The near-infrared (NIR) spectral region is attractive for live-cell imaging, due to low autofluorescence and reduced phototoxicity. Some phytochrome-derived fluorescent proteins absorb and emit fluorescence in the NIR, but have short fluorescence lifetimes and relatively low quantum yields, requiring higher laser powers thus limiting their usefulness for live-cell superresolution microscopy. Using the bacterial phytochrome miRFP703 as a template, we screened for variants with longer fluorescence

Health & MedicineSeptember 25, 2026

Quantitative nanoscale imaging shows peptide-MHC I complexes are monomeric and spatially regulated in human dendritic cells.

Major histocompatibility complex class I (MHC I) molecules present antigenic peptides to cytotoxic T cells, a process central to immune surveillance. However, the nanoscale spatial organization of peptide-MHC I (pMHC I) on human dendritic cells (DCs), key initiators of cytotoxic T cell responses, remains largely unexplored. Here, we combine high-affinity soluble T cell receptors with DNA-based point accumulation for imaging in nanoscale topography (DNA-PAINT) to quantitatively map and count defi

Health & MedicineSeptember 25, 2026

Cannabinoid tolerance relies on CB 1 receptor ubiquitination by NEDD4L.

Cannabinoids, the active components of cannabis, exert numerous acute effects in the brain by engaging cannabinoid CB 1 receptors (CB 1 Rs). However, tolerance emerges rapidly after repeated drug exposure, undermining the efficacy of cannabinoid-based therapies and contributing to cannabis-associated adverse effects. Although the processes of CB 1 R short-term desensitization (i.e., receptor uncoupling and internalization) are well characterized, the mechanisms underlying CB 1 R long-term tolera