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Global greenhouse gas emission, major factor driving climate change, has been increasing since nineteenth century. STIRPAT and CEVSA models were performed to estimate the carbon emission peaks and terrestrial ecosystem carbon sinks at the provincial level in China, respectively. Utilizing the growth characteristics and the peak time criteria for the period 1997-2019, the patterns of energy consumption and CO2 emissions from 30 Chinese provinces are categorized into four groups: (i) one-stage increase (5 provinces), (ii) two-stage increase (10 provinces), (iii) maximum around 2013 (13 provinces), and (iv) maximum around 2017 (2 provinces). According to the STIRPAT model, the anticipated time of peak CO2 emissions for Beijing from the third group is ~ 2025 in both business-as-usual and high-speed scenarios. For Xinjiang Uygur autonomous region from the first group and Zhejiang province from the second group, the expected peak time is 2025 to 2030. Shaanxi province from the fourth group is likely to reach carbon emission peak before 2030. The inventory-based estimate of China's terrestrial carbon sink is ~ 266.2 Tg C/a during the period 1982-2015, offsetting 18.3% of contemporary CO2 emissions. The province-level CO2 emissions, peak emissions and terrestrial carbon sinks estimates presented here are significant for those concerned with carbon neutrality.
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Developing low-cost and high-activity catalysts is one of the keys to promoting the catalytic pyrolysis of waste plastics to fuels for plastic recycling. This work studied the effect of clay as the catalyst on mixed plastic pyrolysis for fuel and energy recovery. Four kinds of clay, including nanoclay, montmorillonite, kaolin, and hydrotalcite, were used as catalysts for the pyrolysis of mixed plastic consisted of polyethylene terephthalate, polystyrene, polypropylene, low-density polyethylene, and high-density polyethylene. The product yield and distribution varied with different clay in pyrolysis. The highest yield of oil was 71.0 % when using montmorillonite as the catalyst. While the highest contents of gasoline range hydrocarbons and diesel range hydrocarbons in the oil were achieved when using kaolin and nanoclay, respectively as catalysts. For the gas products, the CO, C2H4, C2H6, C3H6, and C4H10 increased with decreased CO2 in the gaseous products when using clay as catalysts. In general, the mild acidity of clay catalyst was essential to improve the oil yields and the proportion of the gasoline or diesel range fuels in the catalytic pyrolysis of mixed plastic waste.
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α- and ß-tubulin form heterodimers, with GTPase activity, that assemble into microtubules. Like other GTPases, the nucleotide-bound state of tubulin heterodimers controls whether the molecules are in a biologically active or inactive state. While α-tubulin in the heterodimer is constitutively bound to GTP, ß-tubulin can be bound to either GDP (GDP-tubulin) or GTP (GTP-tubulin). GTP-tubulin hydrolyzes its GTP to GDP following assembly into a microtubule and, upon disassembly, must exchange its bound GDP for GTP to participate in subsequent microtubule polymerization. Tubulin dimers have been shown to exhibit rapid intrinsic nucleotide exchange in vitro, leading to a commonly accepted belief that a tubulin guanine nucleotide exchange factor (GEF) may be unnecessary in cells. Here, we use quantitative binding assays to show that BuGZ, a spindle assembly factor, binds tightly to GDP-tubulin, less tightly to GTP-tubulin, and weakly to microtubules. We further show that BuGZ promotes the incorporation of GTP into tubulin using a nucleotide exchange assay. The discovery of a tubulin GEF suggests a mechanism that may aid rapid microtubule assembly dynamics in cells.
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MOTIVATION: Computational inference of genome organization based on Hi-C sequencing has greatly aided the understanding of chromatin and nuclear organization in three dimensions (3D). However, existing computational methods fail to address the cell population heterogeneity. Here we describe a probabilistic-modeling-based method called CscoreTool-M that infers multiple 3D genome sub-compartments from Hi-C data. RESULTS: The compartment scores inferred using CscoreTool-M represents the probability of a genomic region locating in a specific sub-compartment. Compared to published methods, CscoreTool-M is more accurate in inferring sub-compartments corresponding to both active and repressed chromatin. The compartment scores calculated by CscoreTool-M also help to quantify the levels of heterogeneity in sub-compartment localization within cell populations. By comparing proliferating cells and terminally differentiated non-proliferating cells, we show that the proliferating cells have higher genome organization heterogeneity, which is likely caused by cells at different cell-cycle stages. By analyzing 10 sub-compartments, we found a sub-compartment containing chromatin potentially related to the early-G1 chromatin regions proximal to the nuclear lamina in HCT116 cells, suggesting the method can deconvolve cell cycle stage-specific genome organization among asynchronously dividing cells. Finally, we show that CscoreTool-M can identify sub-compartments that contain genes enriched in housekeeping or cell-type-specific functions. AVAILABILITY AND IMPLEMENTATION: https://github.com/scoutzxb/CscoreTool-M.
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Cromatina , Cromosomas , Genoma , Genómica/métodos , ProbabilidadRESUMEN
Corals form an endosymbiotic relationship with the dinoflagellate algae Symbiodiniaceae, but ocean warming can trigger algal loss, coral bleaching and death, and the degradation of ecosystems. Mitigation of coral death requires a mechanistic understanding of coral-algal endosymbiosis. Here we report an RNA interference (RNAi) method and its application to study genes involved in early steps of endosymbiosis in the soft coral Xenia sp. We show that a host endosymbiotic cell marker called LePin (lectin and kazal protease inhibitor domains) is a secreted Xenia lectin that binds to algae to initiate phagocytosis of the algae and coral immune response modulation. The evolutionary conservation of domains in LePin among marine anthozoans performing endosymbiosis suggests a general role in coral-algal recognition. Our work sheds light on the phagocytic machinery and posits a mechanism for symbiosome formation, helping in efforts to understand and preserve coral-algal relationships in the face of climate change.
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Antozoos , Animales , Antozoos/metabolismo , Ecosistema , Interferencia de ARN , Simbiosis/genética , Análisis de Expresión Génica de una Sola CélulaRESUMEN
In mammalian cell nuclei, the nuclear lamina (NL) underlies the nuclear envelope (NE) to maintain nuclear structure. The nuclear lamins, the major structural components of the NL, are involved in the protection against NE rupture induced by mechanical stress. However, the specific role of the lamins in repair of NE ruptures has not been fully determined. Our analyses using immunofluorescence and live-cell imaging revealed that the nucleoplasmic pool of lamin C rapidly accumulated at sites of NE rupture induced by laser microirradiation in mouse embryonic fibroblasts. The accumulation of lamin C at the rupture sites required both the immunoglobulin-like fold domain that binds to barrier-to-autointegration factor (BAF) and a nuclear localization signal. The accumulation of nuclear BAF and cytoplasmic cyclic GMP-AMP synthase (cGAS) at the rupture sites was in part dependent on lamin A/C. These results suggest that nucleoplasmic lamin C, BAF, and cGAS concertedly accumulate at sites of NE rupture for rapid repair.
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Lamina Tipo A , Membrana Nuclear , Animales , Ratones , Núcleo Celular/metabolismo , Proteínas de Unión al ADN/metabolismo , Fibroblastos/metabolismo , Lamina Tipo A/genética , Lamina Tipo A/metabolismo , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Membrana Nuclear/genética , Membrana Nuclear/metabolismo , Nucleotidiltransferasas/genética , Nucleotidiltransferasas/metabolismoRESUMEN
The chromatin associated with the nuclear lamina (NL) is referred to as lamina-associated domains (LADs). Here, we present an adaptation of the tyramide-signal amplification sequencing (TSA-seq) protocol, which we call chromatin pull down-based TSA-seq (cTSA-seq), that can be used to map chromatin regions at or near the NL from as little as 50 000 cells. The cTSA-seq mapped regions are composed of previously defined LADs and smaller chromatin regions that fall within the Hi-C defined B-compartment containing nuclear peripheral heterochromatin. We used cTSA-seq to map chromatin at or near the assembling NL in cultured cells progressing through early G1. cTSA-seq revealed that the distal ends of chromosomes are near or at the reassembling NL during early G1, a feature similar to those found in senescent cells. We expand the use of cTSA-seq to the mapping of chromatin at or near the NL from fixed-frozen mouse cerebellar tissue sections. This mapping reveals a general conservation of NL-associated chromatin and identifies global and local changes during cerebellar development. The cTSA-seq method reported here is useful for analyzing chromatin at or near the NL from small numbers of cells derived from both in vitro and in vivo sources.
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Cromatina , Mapeo Cromosómico , Lámina Nuclear , Análisis de Secuencia de ADN , Animales , Ratones , Ciclo Celular , Cromatina/genética , Cromatina/metabolismo , Heterocromatina/metabolismo , Lámina Nuclear/metabolismo , Análisis de Secuencia de ADN/métodos , Mapeo Cromosómico/métodosRESUMEN
The ability of a cell to regulate its mechanical properties is central to its function. Emerging evidence suggests that interactions between the cell nucleus and cytoskeleton influence cell mechanics through poorly understood mechanisms. Here we conduct quantitative confocal imaging to show that the loss of A-type lamins tends to increase nuclear and cellular volume while the loss of B-type lamins behaves in the opposite manner. We use fluorescence recovery after photobleaching, atomic force microscopy, optical tweezer microrheology, and traction force microscopy to demonstrate that A-type lamins engage with both F-actin and vimentin intermediate filaments (VIFs) through the linker of nucleoskeleton and cytoskeleton (LINC) complexes to modulate cortical and cytoplasmic stiffness as well as cellular contractility in mouse embryonic fibroblasts (MEFs). In contrast, we show that B-type lamins predominantly interact with VIFs through LINC complexes to regulate cytoplasmic stiffness and contractility. We then propose a physical model mediated by the laminLINC complex that explains these distinct mechanical phenotypes (mechanophenotypes). To verify this model, we use dominant negative constructs and RNA interference to disrupt the LINC complexes that facilitate the interaction of the nucleus with the F-actin and VIF cytoskeletons and show that the loss of these elements results in mechanophenotypes like those observed in MEFs that lack A- or B-type lamin isoforms. Finally, we demonstrate that the loss of each lamin isoform softens the cell nucleus and enhances constricted cell migration but in turn increases migration-induced DNA damage. Together, our findings uncover distinctive roles for each of the four major lamin isoforms in maintaining nucleocytoskeletal interactions and cellular mechanics.
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Fibroblastos , Lámina Nuclear , Animales , Núcleo Celular/metabolismo , Citoesqueleto/metabolismo , Fibroblastos/metabolismo , Lamina Tipo A/genética , Lamina Tipo A/metabolismo , Lamina Tipo B/genética , Lamina Tipo B/metabolismo , Ratones , Lámina Nuclear/metabolismo , Matriz Nuclear/metabolismo , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismoRESUMEN
Intrinsically disordered proteins (IDPs) effect biological function despite their sequence-encoded lack of preference for stable three-dimensional structure. Among their many functions, IDPs form membraneless cellular compartments through liquid-liquid phase separation (LLPS), also termed biomolecular condensation. The extent to which LLPS has been evolutionarily selected remains largely unknown, as the complexities of IDP evolution hamper progress. Unlike structured proteins, rapid sequence divergence typical of IDPs confounds inference of their biophysical or biological functions from comparative sequence analyses. Here, we leverage mitosis as a universal eukaryotic feature to interrogate condensate evolutionary history. We observe that evolution has conserved the ability for six homologs of the mitotic IDP BuGZ to undergo LLPS and to serve the same mitotic function, despite low sequence conservation. We also observe that cellular context may tune LLPS. The phylogenetic correlation of LLPS and mitotic function in one protein raises the possibility of an ancient evolutionary interplay between LLPS and biological function, dating back at least 1.6 billion years to the last common ancestor of plants and animals.
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Proteínas Intrínsecamente Desordenadas , Animales , Proteínas Intrínsecamente Desordenadas/química , FilogeniaRESUMEN
Nuclear lamin isoforms form fibrous meshworks associated with nuclear pore complexes (NPCs). Using datasets prepared from subpixel and segmentation analyses of 3D-structured illumination microscopy images of WT and lamin isoform knockout mouse embryo fibroblasts, we determined with high precision the spatial association of NPCs with specific lamin isoform fibers. These relationships are retained in the enlarged lamin meshworks of Lmna-/- and Lmnb1-/- fibroblast nuclei. Cryo-ET observations reveal that the lamin filaments composing the fibers contact the nucleoplasmic ring of NPCs. Knockdown of the ring-associated nucleoporin ELYS induces NPC clusters that exclude lamin A/C fibers but include LB1 and LB2 fibers. Knockdown of the nucleoporin TPR or NUP153 alters the arrangement of lamin fibers and NPCs. Evidence that the number of NPCs is regulated by specific lamin isoforms is presented. Overall the results demonstrate that lamin isoforms and nucleoporins act together to maintain the normal organization of lamin meshworks and NPCs within the nuclear envelope.
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Simulación por Computador , Embrión de Mamíferos/metabolismo , Fibroblastos/metabolismo , Lamina Tipo A/metabolismo , Lamina Tipo B/metabolismo , Poro Nuclear/metabolismo , Animales , Línea Celular , Embrión de Mamíferos/ultraestructura , Fibroblastos/ultraestructura , Lamina Tipo A/genética , Lamina Tipo B/genética , Ratones , Ratones Noqueados , Poro Nuclear/genética , Poro Nuclear/ultraestructura , Proteínas de Complejo Poro Nuclear/genética , Proteínas de Complejo Poro Nuclear/metabolismoRESUMEN
The nuclear lamina (NL) is a meshwork found beneath the inner nuclear membrane. The study of the NL is hindered by the insolubility of the meshwork and has driven the development of proximity ligation methods to identify the NL-associated/proximal proteins, RNA, and DNA. To simplify and improve temporal labeling, we fused APEX2 to the NL protein lamin-B1 to map proteins, RNA, and DNA. The identified NL-interacting/proximal RNAs show a long 3' UTR bias, a finding consistent with an observed bias toward longer 3' UTRs in genes deregulated in lamin-null cells. A C-rich motif was identified in these 3' UTR. Our APEX2-based proteomics identifies a C-rich motif binding regulatory protein that exhibits altered localization in lamin-null cells. Finally, we use APEX2 to map lamina-associated domains (LADs) during the cell cycle and uncover short, H3K27me3-rich variable LADs. Thus, the APEX2-based tools presented here permit identification of proteomes, transcriptomes, and genome elements associated with or proximal to the NL.
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ADN-(Sitio Apurínico o Apirimidínico) Liasa/metabolismo , Endonucleasas/metabolismo , Enzimas Multifuncionales/metabolismo , Lámina Nuclear/metabolismo , Mapeo de Interacción de Proteínas , Regiones no Traducidas 3'/genética , Secuencia de Bases , ADN-(Sitio Apurínico o Apirimidínico) Liasa/química , Endonucleasas/química , Células HCT116 , Células HEK293 , Humanos , Células K562 , Lamina Tipo B/metabolismo , Enzimas Multifuncionales/química , Dominios Proteicos , Proteoma/metabolismo , ARN/metabolismo , Empalme del ARN/genéticaRESUMEN
Many corals harbour symbiotic dinoflagellate algae. The algae live inside coral cells in a specialized membrane compartment known as the symbiosome, which shares the photosynthetically fixed carbon with coral host cells while host cells provide inorganic carbon to the algae for photosynthesis1. This endosymbiosis-which is critical for the maintenance of coral reef ecosystems-is increasingly threatened by environmental stressors that lead to coral bleaching (that is, the disruption of endosymbiosis), which in turn leads to coral death and the degradation of marine ecosystems2. The molecular pathways that orchestrate the recognition, uptake and maintenance of algae in coral cells remain poorly understood. Here we report the chromosome-level genome assembly of a Xenia species of fast-growing soft coral3, and use this species as a model to investigate coral-alga endosymbiosis. Single-cell RNA sequencing identified 16 cell clusters, including gastrodermal cells and cnidocytes, in Xenia sp. We identified the endosymbiotic cell type, which expresses a distinct set of genes that are implicated in the recognition, phagocytosis and/or endocytosis, and maintenance of algae, as well as in the immune modulation of host coral cells. By coupling Xenia sp. regeneration and single-cell RNA sequencing, we observed a dynamic lineage progression of the endosymbiotic cells. The conserved genes associated with endosymbiosis that are reported here may help to reveal common principles by which different corals take up or lose their endosymbionts.
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Antozoos/citología , Antozoos/genética , Linaje de la Célula/genética , Dinoflagelados/metabolismo , Simbiosis/genética , Animales , Antozoos/inmunología , Antozoos/metabolismo , Carbono/metabolismo , Diferenciación Celular/genética , Arrecifes de Coral , Dinoflagelados/inmunología , Dinoflagelados/fisiología , Ecosistema , Endocitosis , Genoma/genética , Fagocitosis , Fotosíntesis , RNA-Seq , Análisis de la Célula Individual , Simbiosis/inmunología , TranscriptomaRESUMEN
Vibrio parahaemolyticus is a major gastroenteritis-causing pathogen in many Asian countries. Antimicrobial resistance in V. parahaemolyticus has been recognized as a critical threat to food safety. In this study, we determined the prevalence and incidence of antimicrobial resistance in V. parahaemolyticus in the southern Fujian coast, China. A total of 62 isolates were confirmed in retail aquatic products from June to October of 2018. The serotype O3:K6 strains, the virulence genes tdh and trh, antibiotic susceptibility and molecular typing were investigated. Then plasmid profiling analysis and curing experiment were performed for multidrug-resistant strains. The results showed that the total occurrence of V. parahaemolyticus was 31% out of 200 samples. Five strains (8.1%) out of 62 isolates were identified as the V. parahaemolyticus O3:K6 pandemic clone. A large majority of isolates exhibited higher resistance to penicillin (77.4%), oxacillin (71%), ampicillin (66.1%) and vancomycin (59.7%). Seventy-one percent (44/62) of the isolates exhibited multiple antimicrobial resistance. All 62 isolates were grouped into 7 clusters by randomly amplified polymorphic DNA, and most of the isolates (80.6%) were distributed within cluster A. Plasmids were detected in approximately 75% of the isolates, and seven different profiles were observed. Seventy-six percent (25/33) of the isolates carrying the plasmids were eliminated by 0.006% SDS incubated at 42°C, a sublethal condition. The occurrence of multidrug-resistant strains could be an indication of the excessive use of antibiotics in aquaculture farming. The rational use of antimicrobial agents and the surveillance of antibiotic administration may reduce the acquisition of resistance by microorganisms in aquatic ecosystems.
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Antibacterianos/farmacología , Farmacorresistencia Bacteriana/genética , Alimentos Marinos/microbiología , Vibrio parahaemolyticus , Animales , Bivalvos/microbiología , China , Penaeidae/microbiología , Plásmidos/genética , Técnica del ADN Polimorfo Amplificado Aleatorio , Serogrupo , Vibrio parahaemolyticus/clasificación , Vibrio parahaemolyticus/efectos de los fármacos , Vibrio parahaemolyticus/genética , Vibrio parahaemolyticus/aislamiento & purificación , Virulencia/genéticaRESUMEN
RNA-binding proteins with intrinsically disordered regions (IDRs) such as Rbm14 can phase separate in vitro. To what extent the phase separation contributes to their physiological functions is however unclear. Here we show that zebrafish Rbm14 regulates embryonic dorsoventral patterning through phase separation. Zebrafish rbm14 morphants displayed dorsalized phenotypes associated with attenuated BMP signaling. Consistently, depletion of mammalian Rbm14 downregulated BMP regulators and effectors Nanog, Smad4/5, and Id1/2, whereas overexpression of the BMP-related proteins in the morphants significantly restored the developmental defects. Importantly, the IDR of zebrafish Rbm14 demixed into liquid droplets in vitro despite poor sequence conservation with its mammalian counterpart. While its phase separation mutants or IDR failed to rescue the morphants, its chimeric proteins containing an IDR from divergent phase separation proteins were effective. Rbm14 complexed with proteins involved in RNA metabolism and phase separated into cellular ribonucleoprotein compartments. Consistently, RNA deep sequencing analysis on the morphant embryos revealed increased alternative splicing events as well as large-scale transcriptomic downregulations. Our results suggest that Rbm14 functions in ribonucleoprotein compartments through phase separation to modulate multiple aspects of RNA metabolism. Furthermore, IDRs conserve in phase separation ability but not primary sequence and can be functionally interchangeable.
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Through phase separation, some proteins form liquid-like condensates or droplets which can flow, fuse, and even deform when pressure is applied. In some cases, the condensates 'mature' to form gel or solid-like structure. Recent studies suggest that the liquid-like condensates form the structural basis for several membrane-less subcellular organelles such as stress granules and other subcellular structures. Here, we review and discuss studies that implicate protein phase separation in the function of the spindle apparatus and centrosomes.
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Mitosis , Proteínas/metabolismo , Secuencia de Aminoácidos , Animales , Centrosoma/metabolismo , Humanos , Microtúbulos/metabolismo , Orgánulos/metabolismo , Proteínas/química , Huso Acromático/metabolismoRESUMEN
Much effort has been devoted to understand how chromatin modification regulates development and disease. Despite recent progress, however, it remains difficult to obtain high-quality epigenomic maps using chromatin-immunoprecipitation-coupled deep sequencing (ChIP-seq) in samples with low-cell numbers. Here, we present an Atlantis dsDNase-based technology, aFARP-ChIP-seq, that provides accurate profiling of genome-wide histone modifications in as few as 100 cells. By mapping histone lysine trimethylation (H3K4me3) and acetylation (H3K27Ac) in group I innate lymphoid cells (ILC1) sorted from different tissues in parallel, aFARP-ChIP-seq uncovers putative active promoter and enhancer landscapes of several tissue-specific Natural Killer cells (NK) and ILC1. aFARP-ChIP-seq is also highly effective in mapping transcription factor binding sites in small number of cells. Thus, aFARP-ChIP-seq offers multiplexing mapping of both epigenome and transcription factor binding sites using a small number of cells.
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Secuenciación de Inmunoprecipitación de Cromatina/métodos , Linfocitos/citología , Secuenciación Completa del Genoma/métodos , Animales , Recuento de Células , Células Cultivadas , Epigénesis Genética , Femenino , Código de Histonas , Histonas/metabolismo , Linfocitos/metabolismo , Ratones , Células Madre Embrionarias de Ratones/citología , Células Madre Embrionarias de Ratones/metabolismoRESUMEN
Cellular architectural proteins often participate in organ development and maintenance. Although functional decay of some of these proteins during aging is known, the cell-type-specific developmental role and the cause and consequence of their subsequent decay remain to be established especially in mammals. By studying lamins, the nuclear structural proteins, we demonstrate that lamin-B1 functions specifically in the thymic epithelial cells (TECs) for proper thymus organogenesis. An up-regulation of proinflammatory cytokines in the intra-thymic myeloid immune cells during aging accompanies a gradual reduction of lamin-B1 in adult TECs. We show that these cytokines can cause senescence and lamin-B1 reduction of the young adult TECs. Lamin-B1 supports the expression of TEC genes that can help maintain the adult TEC subtypes we identified by single-cell RNA-sequencing, thymic architecture, and function. Thus, structural proteins involved in organ building and maintenance can undergo inflammation-driven decay which can in turn contribute to age-associated organ degeneration.
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Células Epiteliales/metabolismo , Inmunosenescencia/genética , Lamina Tipo B/metabolismo , Timo/crecimiento & desarrollo , Animales , Diferenciación Celular/genética , Citocinas/metabolismo , Femenino , Regulación del Desarrollo de la Expresión Génica/genética , Inflamación/metabolismo , Lamina Tipo B/genética , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Organogénesis/genética , Organogénesis/inmunología , Timo/citología , Regulación hacia Arriba/genéticaRESUMEN
Genome-wide mapping of lamin-B1-genome interactions has shown that gene-poor and transcriptionally inactive genomic regions are associated with the nuclear lamina. Numerous studies have suggested that lamins, the major structural components of the nuclear lamina, play a role in global chromatin organization and gene expression. How lamins could influence the 3D genome organization and transcription from the nuclear periphery has, however, remained unclear. Our recent studies showed that lamins differentially regulate distinct lamina-associated chromatin domains (LADs) at the nuclear periphery, which can in turn influence global 3D genome organization and gene expression. In this Extra View, we discuss how by using various genomics tools, it has become possible to reveal the functions of lamins in orchestrating 3D genome organization and gene expression. Abbreviations: 3D: three dimensional; LAD: lamina-associated chromatin domain; 3C: Chromosome Conformation Capture; TAD: topologically associated domain; HiLands: Histone and lamina landscape; NL: nuclear lamina; mESC: mouse embryonic stem cell; DamID: DNA adenine methyltransferase identification.
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Regulación de la Expresión Génica/genética , Genoma/genética , Laminas/metabolismo , Animales , Núcleo Celular/genética , Núcleo Celular/metabolismo , HumanosRESUMEN
Nuclear lamins are type V intermediate filament proteins. Lamins, including LA, LB1, LB2, and LC, are the major protein components forming the nuclear lamina to support the mechanical stability of the mammalian cell nucleus. Increasing evidence has shown that LA participates in homologous recombination (HR) repair of DNA double-strand breaks (DSBs) . However, the mechanisms underlying this process are incompletely understood. We recently identified the first lamin-binding ligand 1 (LBL1) that directly binds LA and inhibited cancer cell growth. We provided here further mechanistic investigations of LBL1 and revealed that LA interacts with the HR recombinase Rad51 to protect Rad51 from degradation. LBL1 inhibits LA-Rad51 interaction leading to accelerated proteasome-mediated degradation of Rad51, culminating in inhibition of HR repair of DSBs. These results uncover a novel post-translational regulation of Rad51 by LA and suggest that targeting the LA-Rad51 axis may represent a promising strategy to develop cancer therapeutics.