Biology subjects

Kim, J.-S.

Publications and source records attributed to Kim, J.-S..

At least 19 recordsLinked to original sources

bioRxiv2026

Spatial Metabolomics by Desthiobiotin Ligase (DESTNI) in Live Cells

Proximity labeling has transformed spatial proteomics by enabling compartment-resolved mapping of protein environments in living cells, yet its extension to small-molecule metabolites has not been demonstrated, probably due to limitations in labeling chemistry and labeled metabolites identification. Here, we introduce DESTNI, an engineered desthiobiotin (DTB) ligase derived from TurboID through directed evolution, and establish a platform for spatially resolved profiling of amine-containing metabolites. A directed evolution strategy based on a yeast display system yielded DESTNI with efficient DTB-dependent reactivity, enabling robust and compartment-specific proximity labeling across diverse subcellular environments. To identify the DTB-modified amino metabolome, we developed an integrated analytical framework combining DTB-modified amino metabolite standards, in vitro DESTNI profiling, and in silico MS/MS prediction, enabling systematic annotation of DTB-modified amino metabolites. To extend this chemistry to metabolites, we combined synthetic DTB-conjugated metabolite reference standards, in vitro DESTNI-reactive metabolite discovery, and machine-learning prediction of DTB-derivatized metabolites and oligopeptides. Organelle-targeted DESTNI recovered reproducible compartment-enriched amino metabolite signatures, including mitochondrial matrix-enriched glycine, 5-aminolevulinic acid, ornithine and spermidine adducts, as well as nuclear-enriched {gamma}-aminobutyric acid and 5-aminovaleric acid adducts. Together, this work establishes DESTNI as a proximity labeling platform that bridges spatial proteomics and metabolomics and provides a general strategy for mapping subcellular biochemical environments in living cells.

biochemistry↗

bioRxiv2026

Rapid reduction in global chromatin loop size after acute STAG2 reconstitution in human cancer cells

Truncating mutations in the tumor suppressor STAG2, which encodes a component of the cohesin complex, are prevalent across diverse human cancers. Here, we report that acute reconstitution of physiological STAG2 levels in STAG2-mutant human glioblastoma multiforme cancer cells triggers a rapid reduction in the size of chromatin loops genome-wide. Despite this global change in chromatin loop size, early transcriptional responses to STAG2 restoration are limited to a small number of genes, most of which are induced by STAG2 reconstitution. Notably, the growth-suppressor EFEMP1 (Fibulin-3), a secreted glycoprotein that functions as an extracellular matrix-associated inhibitor of glioblastoma growth and invasion, was the only gene consistently induced across all experimental models. The most robust and conserved STAG2-induced genes all reside within intense chromatin loops whose anchors and overall intensity did not appear to change in response to STAG2 reconstitution. These findings suggest that inactivating mutations of STAG2 promote neoplastic transformation by alleviating a restriction on chromatin loop size, allowing for an expanded range of chromatin interactions that disrupts the maintenance of a tumor-suppressive transcriptome.

cancer biology↗

bioRxiv2026

Telomere-to-telomere, accurate, and gapless genome assembly (TTAGGA) of the Korean Jindo dog with a single-contig Y chromosome

Complete canine reference genomes are essential for studies of structural variation, sex-chromosome evolution, and breed-specific architecture, yet existing references remain incomplete on the Y chromosome and retain internal gaps across multiple chromosomes. Here, we introduce TTAGGA (Telomere-to-Telomere, Accurate, Gapless Genome Assembly), a stricter completeness standard requiring chromosomes assembled end-to-end with zero internal gaps and Merqury consensus QV [≥] 50, and present Jindo1-G-TTAGGA, the first canine assembly to meet this standard, achieved under a stringent QV [≥] 60 threshold. From 813 Gb ([~]340x coverage) of multi-platform data (PacBio HiFi [~]150x, ONT ultra-long [~]103x, parental Illumina [~]40x per parent) generated from a male Korean Jindo dog, trio binning with hifiasm produced two haplotype-resolved assemblies of 2,441.6 Mb (Hap1, maternal, chrX-carrying) and 2,340.5 Mb (Hap2, paternal, chrY-carrying). Both haplotypes are gap-free at every internal position, with canonical telomeric repeats verified at both ends of all 39 chromosomes (tidk), Merqury consensus QV of 78.0 (Hap1) and 76.8 (Hap2), trio switch-error rates below 0.13%, BUSCO completeness of 99.3% (Hap1) and 96.4% (Hap2; the lower value reflects absent X-linked orthologues in the Y-bearing haplotype), and Genome Continuity Index values of 98.2 (Hap1) and 94.7 (Hap2). Hap2 carries a single 21,255,890 bp gap-free Y chromosome with TTAGGG telomeric repeats at the q-arm terminus and an acrocentric satellite-rich p-arm, representing a 5.4-fold increase over the 3.94 Mb chrY of ROS_Cfam_1.0 and adding approximately 14 Mb of newly resolved Y-linked sequence; this corresponds to roughly 79% of the cytogenetically estimated 27 Mb full-length canine chrY. Jindo1-G-TTAGGA provides a chromosome-scale, haplotype-resolved, gap-free canine reference for studies of canine structural variation, sex-chromosome evolution, and canid phylogenomics.

genomics↗

bioRxiv2026

Endogenous nucleophilic scavengers of reactive acyl-species neutralize carbon stress

Aberrant protein acylation by reactive acyl species (RAS)--termed carbon stress--is a major driver of aging and metabolic disease. While enzymatic deacylases such as sirtuins counteract aberrant acylation, whether endogenous metabolites can directly neutralize RAS remains unclear. Here, we report that nucleophilic metabolites--taurine, spermidine, and ethanolamine--react with acyl-CoAs, preventing aberrant protein acylation and potentially extending lifespan. We demonstrate that spermidine scavenges acetyl-CoA within the catalytic pocket of p300, a histone acetyltransferase, and extends lifespan in Drosophila. Taurine supplementation in mice fed a high-fat diet promotes N-fatty acyl taurine formation, confirming in vivo scavenging of RAS. These findings identify endogenous nucleophilic metabolites as scavengers that neutralize carbon stress, with implications for combating aging and metabolic disease. SummaryProtein homeostasis is constantly challenged by reactive metabolic intermediates that drive aberrant post-translational modifications, contributing to aging and metabolic disease. While the antioxidant systems that neutralize reactive oxygen species (ROS) are well characterized, whether analogous defenses exist against reactive acyl species (RAS)--the metabolic drivers of non-enzymatic protein acylation, termed carbon stress--has remained unknown. Here we show that three abundant endogenous nucleophilic metabolites--taurine, spermidine, and ethanolamine--directly intercept reactive acyl-CoA species through nucleophilic attack, preventing aberrant protein acylation. We demonstrate that spermidine scavenges acetyl-CoA within the catalytic pocket of the histone acetyltransferase p300, effectively buffering p300-mediated hyperacetylation of muscle, cytosolic, and mitochondrial proteins and extending lifespan in a Drosophila model of p300-driven toxicity. In mice fed a high-fat diet, taurine supplementation promotes the formation of N-fatty acyl taurines, providing direct in vivo evidence for nucleophilic scavenging of diet-derived RAS. Our findings reveal a previously unrecognized metabolite-based defense system--parallel to classical antioxidant defenses against ROS--that neutralizes carbon stress, with broad implications for understanding the molecular mechanisms of aging and the long-observed but mechanistically unexplained health benefits of taurine and spermidine.

biochemistry↗

bioRxiv2026

MitoAtlas: a Domain-Resolved Spatial Map of the HumanMitochondrial Proteome

Mitochondrial function depends on the precise sub-organellar localization and topological orientation of its proteome. However, mapping this architecture with domain-level precision across the double-membrane system has remained challenging. Here, we present MitoAtlas, a spatial systems biology resource built on SR-PL (super-resolution proximity labeling) that resolves the sub-mitochondrial architecture of 861 proteins at domain-level resolution. By deploying 42 spatially restricted APEX2 and BioID/BioID2 baits across mitochondrial compartments and cytosol in HEK293T-REx cells, we mapped 13,440 unique proximity-labeled sites. Integrating high-density spatial data with a machine-learning classification pipeline and AlphaFold structural modeling, we resolved membrane topologies for 196 transmembrane proteins and assigned sub-mitochondrial localizations to 160 previously unannotated mitochondrial proteins absent from MitoCarta3.0, including MINPP1 as an intermembrane space resident. Coupling bait-specific proximity labeling signatures with AlphaFold structure prediction and metabolite docking identified 47 protein-protein interactions, including the LETM1-Citrate Synthase complex, and 155 protein-metabolite interactions. MitoAtlas is available at mitoatlas.org as a domain-resolution spatial map of mitochondrial architecture and metabolism.

cell biology↗

bioRxiv2026

PersonaAI: An Interactive Agentic-AI Framework for Autonomous Hypothesis Generation and Validation in Aging

Elucidating the mechanisms of aging is impeded by its stochastic, multi-scale nature and cellular heterogeneity, challenges that are compounded by the overwhelming volume of biomedical literature and the complexity of genome-wide datasets. To overcome these barriers, we present PersonaAI, an interactive agentic-AI framework that acts as a digital co-scientist. By integrating literature-based reasoning with autonomous in silico validation, PersonaAI synthesizes over 560,000 aging-related publications via retrieval-augmented generation (RAG) to propose mechanistic hypotheses. These hypotheses are subsequently validated by autonomous agents utilizing single-cell RNA-seq data. Using a temporal cutoff strategy restricted to pre-2020 literature, we demonstrate that PersonaAI can generate hypotheses effectively validated by post-2021 discoveries, proving its capacity for inference beyond simple information retrieval. In application, the system identified senescent Cirbp+ hepatocytes as a liver-intrinsic aging program and uncovered a middle-aged, male-specific decline in adipose stem and progenitor cells, driven by vascular niche deterioration and disrupted VEGF-VEGFR signaling. These results establish PersonaAI as a scalable platform that augments human intuition with autonomous data-driven validation, providing a generalizable platform for accelerating discovery in aging biology.

bioinformatics↗

bioRxiv2025

Copper deficiency disrupts OXPHOS and mitochondrial dynamics through MTCH2-dependent copper trafficking in skeletal muscle

Copper is an essential trace element for mitochondrial respiration and cellular metabolism, yet its physiological role in skeletal muscle remains incompletely understood. Here, we show that skeletal muscle-specific deletion of the high-affinity copper importer Ctr1 (SMKO) in mice causes local copper deficiency, resulting in exercise intolerance, systemic metabolic dysfunction, and hallmarks of mitochondrial myopathy such as ragged-red fibers, lactic acidosis, and aberrant mitochondrial morphology. Mechanistically, copper starvation disrupted the electron transport chain proteome and drove pathological mitochondrial hyperfusion. We identified mitochondrial carrier homolog 2 (MTCH2), an outer mitochondrial membrane protein, as a copper-binding regulator that coordinates mitochondrial copper distribution and morphology. Restoring copper levels via a copper ionophore or AAV-mediated Ctr1 re-expression rescued mitochondrial function and alleviated myopathic features in SMKO. These findings uncover the functional coupling of CTR1 and MTCH2 as a critical mechanistic link between copper homeostasis and mitochondrial remodeling required for skeletal muscle function.

molecular biology↗

bioRxiv2025

BOGO: A Proteome-Wide Gene Overexpression Platform for Discovering Rational Cancer Combination Therapies

O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/673780v2_ufig1.gif" ALT="Figure 1"> View larger version (56K): org.highwire.dtl.DTLVardef@19d5d7dorg.highwire.dtl.DTLVardef@64f7eborg.highwire.dtl.DTLVardef@d08b75org.highwire.dtl.DTLVardef@173c448_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical AbstractC_FLOATNO C_FIG Cancer drug resistance remains a major barrier to durable treatment success, often leading to relapse despite advances in precision oncology. While combination therapies are being increasingly investigated, such as chemotherapy with small molecule inhibitors, predicting drug response and identifying rational drug combinations based on resistance mechanisms remain major challenges. Therefore, a proteome-wide, single-gene overexpression screening platform is essential for guiding rational therapy selection. Here, we present BOGO (Bxb1-landing pad human ORFeome-integrated system for a proteome-wide Gene Overexpression), a robust, scalable, and reproducible screening platform that enables single-copy, site-specific integration and overexpression of [~]19,000 human open across cancer cell models. Using BOGO, we identified drug-specific response drivers for 16 chemotherapeutic agents and integrated clinical datasets to uncover proliferation and resistance-associated genes with prognostic potential. Drug response similarity networks revealed both shared and unique mechanisms, highlighting key pathways such as autophagy, apoptosis, and Wnt signaling, and notable resistance-associated genes including BCL2, POLD2, and TRADD. In particular, we proposed a synergistic combination of the BCL2 family inhibitor ABT-263 (Navitoclax(R)) and the DNA analog TAS-102 (Lonsurf(R)), which revealed that lysosomal modulation is a key mechanism driving DNA analog resistance. This combination therapy selectively enhanced cytotoxicity in colorectal and pancreatic cancer cells in vitro, and demonstrated therapeutic benefit in vivo in both cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) models. Together, these findings establish BOGO as a powerful gene overexpression perturbation platform for systematically identifying chemoresistance and chemosensitization drivers, and for discovering rational combination therapies. Its scalability and reproducibility position BOGO as a broadly applicable tool for functional genomics and therapeutic discovery beyond cancer resistance.

systems biology↗

bioRxiv2024

Structural basis of the catalytic and allosteric mechanism of bacterial acetyltransferase PatZ

GCN5-related N-Acetyltransferases (GNATs) play a crucial role in regulating bacterial metabolism by acetylating specific target proteins. Despite their importance in bacterial physiology, the mechanisms underlying GNATs enzymatic and regulatory functions remain poorly understood. In this study, we elucidated the structures of Escherichia coli PatZ, a type I GNAT, and investigated its ligand interactions, catalytic processes, and allosterism. PatZ functions as a homotetramer, with each subunit comprising a catalytic domain and a regulatory domain. Our findings reveal that the regulatory domain is essential for acetyltransferase activity, as it not only induces cooperative conformational changes in the catalytic domain but also directly contributes to the formation of substrate binding pockets. Furthermore, a protein structure-based analysis on the evolution of bacterial GNAT types reveals a distinct pattern of the regulatory domain across phyla, underscoring the regulatory domains critical role in responding to cellular energy status. SIGNIFICANCE STATEMENTPost-translational modifications, particularly acetylation mediated by GCN5-related N-Acetyltransferases (GNATs), play a crucial role in bacterial physiology. Protein acetyltransferase Z (PatZ) is a key GNAT with diverse substrates, essential for understanding the bacterial acetylome. This study employs cryogenic electron microscopy, X-ray crystallography, and biochemical analyses to elucidate the mechanistic regulation of Escherichia coli PatZ. Our high-resolution structures reveal PatZs homo-tetrameric architecture, with each subunit comprising regulatory and GNAT domains. We characterize ligand-PatZ interactions, demonstrating ligand-induced conformational changes that facilitate allosteric regulation of the catalytic domain. Furthermore, our analyses elucidate the regulatory domains contribution to substrate binding pocket formation, potentially enhancing substrate specificity. Structure-based phylogenetic analysis provides insights into the evolution of diverse regulatory domains in the GNAT superfamily across bacterial taxonomy. This first visualization of PatZ advances our mechanistic understanding of bacterial physiology, offering novel insights into GNAT-mediated bacterial adaptations. HIGHLIGHTS- E. coli PatZ forms a homotetramer, with each subunit possessing a GNAT catalytic domain and a regulatory domain. - Cooperative binding of acetyl-CoA to the regulatory domains is a prerequisite for inducing the structural compatibility of the catalytic domain with a substrate. - Diverse regulatory domains in GNATs evolved to adapt to varied metabolic conditions across bacterial taxonomy.

biochemistry↗

bioRxiv2024

Serpina1e mediates the exercise-induced enhancement of hippocampal memory

The exercise-induced enhancement of learning and memory is thought to be regulated by body{square}brain interactions via secretory proteins in the blood plasma1,2. Given the prominent role that skeletal muscle plays during exercise, the beneficial effects of exercise on cognitive functions appear to be mediated by muscle-derived secretory factors including myokines3,4. However, the specific myokines that exert beneficial effects on cognitive functions remain to be elucidated. Here, we reveal that a novel myokine, Serpina1e, acts a molecular mediator that directly supports long-term memory formation in the hippocampus. Using an in vivo myokine-labeling mouse model, proteomic analysis revealed that the Serpina1 family of proteins are the myokines whose levels increased the most in plasma after chronic aerobic exercise for 4 weeks. Systemic delivery of recombinant Serpina1e into sedentary mice was sufficient for reproducing the beneficial effect of exercise on hippocampus-associated cognitive functions. Moreover, plasma Serpina1e can cross the blood-cerebral spinal fluid (CSF) barrier and blood-brain barrier to reach the brain, thereby influencing hippocampal function. Indeed, an increase in the plasma level of Serpina1e promoted hippocampal neurogenesis, increased the levels of brain-derived neurotrophic factor (BDNF) and induced neurite growth. Our findings reveal that Serpina1e is a myokine that migrates to the brain and mediates exercise-induced memory enhancement by triggering neurotrophic growth signaling in the hippocampus. This discovery elucidates the molecular mechanisms underlying the beneficial effects of exercise on cognitive function and may have implications for the development of novel therapeutic interventions for alleviating cognitive disorders.

neuroscience↗

bioRxiv2024

Multiomics-based assessment of the impact of airflow on diverse plant callus cultures

Plant cell culture has multiple applications in biotechnology and horticulture, from plant propagation to the production of high-value biomolecules. However, the interplay between cellular diversity and ambient conditions influences the metabolism of cultured tissues; understanding these factors in detail will inform efforts to optimize culture conditions. This study presents multiomics datasets from callus cultures of tobacco (Nicotiana tabacum), rice (Oryza sativa), and two bamboo species (Phyllostachys nigra and P. bambusoides). Over four weeks, calli were cultured under continuous moisture without airflow or gradually reduced ambient moisture with airflow. For each sample, gene expression was profiled with high-throughput RNA sequencing, 442 metabolites were measured using liquid chromatography (LC) with triple-quadrupole mass spectrometry (LC-QqQMS), and 31 phytohormones were quantified using ultra-performance LC coupled with a tandem quadrupole mass spectrometer equipped with an electrospray interface (UPLC-ESI-qMS/MS) and ultra-high-performance LC- orbitrap MS (UHPLC-Orbitrap MS). These datasets highlight the impact of airflow on callus cultures, revealing differences between and within species, and provide a comprehensive resource to explore the physiology of callus growth.

plant biology↗

bioRxiv2024

Cellular dsRNA interactome reveals the regulatory map of exogenous RNA sensing

RNA-binding proteins (RBPs) provide a critical post-transcriptional regulatory layer in determining RNA fate. Currently, UV crosslinking followed by oligo-dT pull-down is the golden standard in identifying the RBP repertoire, but such method is ineffective in capturing RBPs that recognize double-stranded RNAs (dsRNAs). Here, we utilize anti-dsRNA antibody immunoprecipitation followed by quantitative mass spectrometry to comprehensively identify RBPs bound to cellular dsRNAs without any external stimulus. Notably, our dsRNA interactome contains proteins involved in sensing N6-methyladenosine RNAs and stress granule components. We further perform targeted CRISPR-Cas9 knockout functional screening and discover proteins that can regulate the interferon (IFN) response during exogenous RNA sensing. Interestingly, depleting dsRBPs mostly attenuate the IFN response, and they act as antiviral factors during human {beta}-coronavirus HCoV-OC43 infection. Our dsRNA interactome capture provides an unbiased and comprehensive characterization of putative dsRBPs and will facilitate our understanding of dsRNA sensing in both physiological and pathological contexts.

molecular biology↗

bioRxiv2023

Monocyte-derived microglia with Dnmt3a mutation cause motor pathology in aging mice

Microglia are established in embryogenesis forming a self-containing cellular compartment resisting seeding with cells derived from adult definitive hematopoiesis. We report that monocyte-derived macrophages (MoM{Phi}) accumulate in the brain of aging mice with distinct topology, including the nigrostriatum and medulla, but not the frontal cortex. Parenchymal MoM{Phi} adopt bona fide microglia expression profiles. Unlike microglia, these monocyte-derived microglia (MoMg) are due to their hematopoietic origin targets of clonal hematopoiesis (CH). Using a chimeric transfer model, we show that hematopoietic expression of DNMT3AR822H, a prominent mutation in human CH, renders MoMg pathogenic promoting motor deficits resembling atypical Parkinsonian disorders. Collectively, these data establish in a mouse model that MoMg progressively seed the brains of aging healthy mice, accumulate in selected areas, and, when carrying a somatic mutation associated with CH, can contribute to brain pathology.

immunology↗

bioRxiv2023

Engineering TALE-linked deaminases to facilitate precision adenine base editing in mitochondrial DNA

DddA-derived cytosine base editors (DdCBEs) and transcription activator-like effector (TALE)-linked deaminases (TALEDs) catalyze targeted base editing of mitochondrial DNA (mtDNA) in eukaryotic cells, a method useful for modeling of mitochondrial genetic disorders and developing novel therapeutic modalities. Here, we report that A-to-G editing TALEDs but not C-to-T editing DdCBEs induce tens of thousands of transcriptome-wide off-target edits in human cells. To avoid these unwanted RNA edits, we engineered the substrate-binding site in TadA8e, the deoxy-adenine deaminase in TALEDs, and created TALED variants with fine-tuned deaminase activity. Our engineered TALED variants not only reduced RNA off-target edits by > 99% but also minimized off-target mtDNA mutations and bystander edits at a target site. Unlike wild-type versions, our TALED variants were not cytotoxic and did not cause developmental arrest of mouse embryos. As a result, we obtained mice with pathogenic mtDNA mutations, associated with Leigh disease, which showed reduced heart rates.

molecular biology↗

bioRxiv2023

Murine classical monocyte subsets display distinct functions and fates

Monocytes are short-lived myeloid immune cells that arise from adult hematopoiesis and circulate for a short time in the blood. They comprise two main subsets, in mice defined as classical Ly6Chigh and non-classical Ly6Clow monocytes (CM, NCM). Recent fate mapping and transcriptomic analyses revealed that CM themselves are heterogeneous. Here, we report surface markers that allow segregation of murine GMP- and MDP-derived CM in the BM and blood. Functional characterization, including fate definition following adoptive cell transfer, established that GMP-Mo and MDP-Mo could equal rise to homeostatic CM progeny, such as NCM in blood and gut macrophages, but differentially seeded selected other tissues. Specifically, GMP-Mo and MDP-Mo gave rise to distinct interstitial lung macrophages, thus linking CM dichotomy to previously reported pulmonary macrophage heterogeneity. Collectively, we provide comprehensive evidence for the existence of two functionally distinct CM subsets in the mouse, which differentially contribute to peripheral tissue macrophage populations in homeostasis and following challenge. Our findings are indicative of impact of monocyte ontogeny on in situ differentiation.

immunology↗

bioRxiv2022

Sniper2L, a high-fidelity Cas9 variant with high activity

Although several high-fidelity SpCas9 variants that have reduced activities at mismatched target sequences have been reported, it has been observed that this increased specificity is associated with reduced on-target activity, limiting the applications of the high-fidelity variants when efficient genome editing is required. Here, we developed an improved version of Sniper-Cas9, Sniper2L, which represents an exception to this trade-off trend as it showed higher specificity with retained high activity. We evaluated Sniper2L activities at a large number of target sequences, and developed DeepSniper, a deep-learning model that can predict the activity of Sniper2L. We also confirmed that Sniper2L can induce highly efficient and specific editing at a large number of target sequences when it is delivered as a ribonucleoprotein complex. Mechanically, the high specificity of Sniper2L originates from its superior ability to avoid unwinding a target DNA containing even a single mismatch. We envision that Sniper2L will be useful when efficient and specific genome editing is required.

bioengineering↗

bioRxiv2022

Oocytes can repair DNA damage during meiosis via a microtubule-dependent recruitment of CIP2A-MDC1-TOPBP1 complex from spindle pole to chromosomes

Because DNA double-strand breaks (DSBs) greatly threaten genomic integrity, effective DNA damage sensing and repair are essential for cellular survival in all organisms. However, DSB repair mainly occurs during the interphase and is repressed during mitosis. Here, we show that, unlike mitotic cells, oocytes can repair DSBs during meiosis through microtubule-dependent chromosomal recruitment of the CIP2A-MDC1-TOPBP1 complex from spindle poles. After DSB induction, we observed spindle shrinkage and stabilization, as well as BRCA1 and 53BP1 recruitment to chromosomes and subsequent DSB repair during meiosis I. Moreover, p-MDC1 and p-TOPBP1 were recruited from spindle poles to chromosomes in a CIP2A-dependent manner. This pole-to-chromosome relocation of the CIP2A-MDC1-TOPBP1 complex was impaired not only by depolymerizing microtubules but also by depleting CENP-A or HEC1, indicating that the kinetochore/centromere serves as a structural hub for microtubule-dependent transport of the CIP2A-MDC1-TOPBP1 complex. Mechanistically, DSB-induced CIP2A-MDC1-TOPBP1 relocation is regulated by PLK1 but not by ATM activity. Our data provide new insights into the critical crosstalk between chromosomes and spindle microtubules in response to DNA damage to maintain genomic stability during oocyte meiosis.

cell biology↗

bioRxiv2022

Mid-summer snow-free albedo across the Arctic tundra was mostly stable or increased over the past two decades

Arctic vegetation changes, such as increasing shrub-cover, are expected to accelerate climate warming through increased absorption of incoming radiation and corresponding decrease in summer shortwave albedo. Here we analyze mid-summer shortwave land-surface albedo and its change across the pan-Arctic region based on MODIS satellite observations over the past two decades (2000-2021). In contrast to expectations, we show that terrestrial mid-summer shortwave albedo has not significantly changed in 82% of the pan-Arctic region, while 14% show an increase and 4% a decrease. By analyzing the visible and near-/shortwave-infrared range separately, we demonstrate that the slight increase arises from an albedo increase in the near-/shortwave-infrared range domain while being partly compensated by a decrease in visible albedo. A similar response was found across different tundra vegetation types. We argue that this increase in reflectance is typical with increasing biomass as a result of increased multiple reflection in the canopy. However, CMIP6 global climate model albedo predictions showed the opposite sign and different spatial patterns of snow-free summer albedo change compared to satellite-derived results. We suggest that a more sophisticated vegetation parametrization can reduce this discrepancy, and provide albedo estimates per vegetation type.

ecology↗