Nuclear Envelope Dynamics in Dictyostelium Amoebae

Cells, Journal Year: 2025, Volume and Issue: 14(3), P. 186 - 186

Published: Jan. 26, 2025

In the last decades, study of many nuclear envelope components in Dictyostelium amoebae has revealed conserved mechanisms dynamics that root back unexpectedly deep into eukaryotic tree life. this review, we describe state art research organism starting from early work on pore complexes to characterization first true lamin a non-metazoan and its associated transmembrane proteins, such as HeH-family protein Src1 LINC complex Sun1. We also dynamic processes during semi-closed mitosis, including centrosome insertion envelope, involved restoration permeability around mitotic exit compare them situation cells with open or fully closed mitosis.

Language: Английский

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Roles for the 3D genome in the cell cycle, DNA replication, and double strand break repair

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13

Published: Feb. 27, 2025

Large eukaryotic genomes are packaged into the restricted area of nucleus to protect genetic code and provide a dedicated environment read, copy repair DNA. The physical organisation genome chromatin loops self-interacting domains provides basic structural units architecture. These arrangements complex, multi-layered, highly dynamic influence how different regions interact. role structures during transcription via enhancer-promoter interactions is well established. Less understood nuclear architecture influences plethora transactions DNA replication repair. In this review, we discuss regulated cell cycle positioning origins coordination double strand break in these cellular processes highlights its critical involvement preserving integrity cancer prevention.

Language: Английский

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A high throughput, high content screen for non-toxic small molecules that reduce levels of the nuclear lamina protein, Lamin B1

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: March 1, 2025

Lamin B1 (LMNB1) is an intermediate filament protein that integral component of the nuclear lamina, a structure critical for organization and function. Mutations involving lamin gene cause adult-onset demyelinating disorder, Autosomal Dominant Leukodystrophy (ADLD) which charactered by increased expression. Increased LMNB1 expression also associated with poorer outcomes in multiple cancer subtypes. Reducing thus attractive therapeutic pathway ADLD potentially other diseases. Here we present results high throughput / content screen (HTS/HCS) to identify small molecules reduce levels. Approximately 97,000 were screened using inducible mouse fibroblast model overexpression have previously generated. Two molecules, Pubchem CID 662896 5308648, identified reduced dose dependent manner without causing cellular toxicity corrected abnormalities overexpression, hallmark ADLD. levels patient samples, exhibited favorable "drug-like" physicochemical properties crossed blood brain barrier studies. While may be promising candidate therapy, further investigations are required determine its mechanism action ability target disease relevant cell types.

Language: Английский

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Nuclear warfare: pathogen manipulation of the nuclear pore complex and nuclear functions

mBio, Journal Year: 2025, Volume and Issue: unknown

Published: March 20, 2025

ABSTRACT Viruses and bacteria exploit the nuclear pore complex (NPC) host functions to bypass cellular barriers manipulate essential processes. frequently engage directly with NPC components, such as nucleoporins, enable genome import evade immune defenses. In contrast, bacterial pathogens rely on secreted effector proteins disrupt transport reprogram transcription. These strategies reflect a remarkable evolutionary convergence, both types of targeting promote infection. This minireview explores overlapping unique mechanisms by which hijack nucleus, shedding light their roles in disease potential avenues for therapeutic intervention.

Language: Английский

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The Dilemma of Nuclear Mechanical Forces in DNA Damage and Repair

Biochemical and Biophysical Research Communications, Journal Year: 2025, Volume and Issue: unknown, P. 151639 - 151639

Published: March 1, 2025

Language: Английский

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Effects of mutant lamins on nucleo-cytoskeletal coupling in Drosophila models of LMNA muscular dystrophy

Frontiers in Cell and Developmental Biology, Journal Year: 2022, Volume and Issue: 10

Published: Aug. 31, 2022

The nuclei of multinucleated skeletal muscles experience substantial external force during development and muscle contraction. Protection from such forces is partly provided by lamins, intermediate filaments that form a scaffold lining the inner nuclear membrane. Lamins play myriad roles, including maintenance shape stability, mediation mechanoresponses, nucleo-cytoskeletal coupling. Herein, we investigate how disease-causing mutant lamins alter myonuclear properties in response to mechanical force. This was accomplished

Language: Английский

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The molecular basis of lamin-specific chromatin interactions

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 5, 2024

Abstract In the cell nucleus, chromatin is anchored to nuclear lamina, a network of lamin filaments and binding proteins that underly inner membrane. The lamina involved in organisation through interaction lamina-associated domains (LADs) within densely packed heterochromatin regions. Employing cryo-focused ion beam (cryo-FIB) milling conjunction with cryo-electron tomography (cryo-ET), we analysed distribution nucleosomes at lamin-chromatin interface. Depletion A/C reduced concentration periphery, suggesting lamins are directly chromatin. Using microscopy (cryo-EM), then identified specific motif A tail domain interacts nucleosomes, distinguishing it from other isoforms. Furthermore, examined structure dynamics using genome-wide analysis revealed lamin-dependent macroscopic-scale alterations gene expression remodelling. Our findings provide detailed insights into dynamic structural interplay between isoforms chromatin, molecular interactions which shaping architecture epigenetic regulation.

Language: Английский

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Thymopoietin‐α, ‐β, and ‐γ Isoforms Increased Expression in Cervical Cancer Cells

Canadian Journal of Infectious Diseases and Medical Microbiology, Journal Year: 2025, Volume and Issue: 2025(1)

Published: Jan. 1, 2025

Cervical cancer (CC) is a public health concern related to the human papillomavirus (HPV) persistent infection. Minichromosome maintenance 2 (MCM2) has been postulated as surrogate marker for HPV Thymopoietin (TMPO) nuclear protein regulated by E2F such MCM2 or p16. TMPO can give rise six different isoforms. Herein, both mRNA and levels of isoforms were analyzed in cervical cells. expression was selected through silico several databases from healthy cervix lesions. RNA evaluated samples cell lines RT-PCR Western-blot immunohistochemistry assays. immunostaining smears. The clinical-pathological correlation analysis performed using Kruskal-Wallis Χ tests. overexpressed 74% CC cells all lines. Moreover, negative observed normal tissue, compared strong Interestingly, TMPO-α, -β, -δ, -ε, -γ are expressed tissues, but differential α, among when present. Also, quite similar, more sensitive specific than protein. present study revealed that could be potential molecular transformed cells, highlighting promising

Language: Английский

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Molecular Mechanisms for the Regulation of Nuclear Membrane Integrity

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(20), P. 15497 - 15497

Published: Oct. 23, 2023

The nuclear membrane serves a critical role in protecting the contents of nucleus and facilitating material signal exchange between cytoplasm. While extensive research has been dedicated to topics such as assembly disassembly during cell division, well interactions transmembrane proteins both nucleoskeletal cytoskeletal components, there comparatively less emphasis on exploring regulation morphology through integrity. In particular, type II integral proteins, which also function transcription factors, within remains an area that is yet be fully explored. integrity pivotal not only division but gene expression communication Importantly, it plays significant development various diseases. This review paper seeks illuminate biomolecules responsible for maintaining membrane. It will delve into mechanisms influence provide insights protein factors this context. Understanding these aspects utmost importance, can offer valuable intricate processes governing Such have broad-reaching implications cellular our understanding disease pathogenesis.

Language: Английский

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Phosphorylation of Lamin A/C regulates structural integrity of the nuclear envelope

Journal of Biological Chemistry, Journal Year: 2024, Volume and Issue: 301(1), P. 108033 - 108033

Published: Nov. 28, 2024

Dynamic disassembly and reconstruction of the nuclear lamina during entry exit mitosis, respectively, are pivotal steps in proliferation higher eukaryotic cells. Although numerous post-translational modifications lamin proteins have been identified, key factors driving dynamics remain elusive. Here we identified CDK1-elicited phosphorylation sites on endogenous Lamin A/C characterized their functions regulation lamina. Specifically, mass spectrometry revealed CDK1-mediated at N-terminal Thr19/Ser22 C-terminal Ser390/Ser392 mitosis. Importantly, phospho-mimicking 4D mutant T19D/S22D/S390D/S392D completely disrupted A filamentous structure interphase Conversely, non-phosphorylatable T19A/S22A especially 4A T19A/S22A/S390A/S392A protected from depolymerization These results suggest that dephosphorylation both N- regulate dynamics. Engineering into LMNA gene resulted abnormalities micronucleus formation telophase. Perturbation is shown to prevent proper envelope impair integrity. findings reveal a previously undefined link between dynamics, plasticity, genomic stability cell cycle.

Language: Английский

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