Interdependence between Nuclear Pore Gatekeepers and Genome Caretakers: Cues from Genome Instability Syndromes DOI Open Access
Lidia Larizza, Elisa Adele Colombo

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(17), P. 9387 - 9387

Published: Aug. 29, 2024

This review starts off with the first germline homozygous variants of Nucleoporin 98 gene (NUP98) in siblings whose clinical presentation recalls Rothmund–Thomson (RTS) and Werner (WS) syndromes. The progeroid phenotype caused by a associated haematological malignancies neurodegenerative disorders primed search for interplay between caretakers involved genome instability syndromes Nuclear Pore Complex (NPC) components. In context basic information on NPC architecture functions, we discuss studies interdependence gatekeepers WS Hereditary Fibrosing Poikiloderma (POIKTMP), both entering differential diagnosis RTS. WS, WRN/WRNIP complex interacts nucleoporins Y-complex NDC1 altering architecture. POIKTMP, mutated FAM111B, recruited Y-complex’s SEC13 NUP96, several Nups safeguarding structure. linkage defective to highlights attempt activate repair hub at nuclear periphery restore DNA damage. two separate POIKTMP are drawn close interaction their damage sensors shared hallmark short fragile telomeres disclosing major role telomere maintenance.

Language: Английский

Radiation symptoms resemble laminopathies and the physical underlying cause may sit at the lamin A C-terminus DOI Creative Commons

A Waldherr,

Anna Fogtman

Molecular Medicine, Journal Year: 2025, Volume and Issue: 31(1)

Published: Feb. 20, 2025

Ionizing radiation causes three divergent effects in the human body: On one side, tissue death (= deterministic effects) sets on, on other mutations and cancer growth stochastic can occur. In recent years, additional phenomenon of accelerated aging has come to light. following, we argue that these seemingly contradictory responses namely: (i) increased growth, (ii) ablation or (iii) senescence, share an underlying cause from damage at lamin A C-terminus. words, besides typically described genomic impact, propose destabilization pathway via oxidation nuclear envelope. We five concrete hypotheses draw a direct mechanistic model cellular oxidative stress, micronuclei clinical symptoms. conjunction with B compensation, might be able explain why dominate. If our holds true, novel target for radiotherapeutics radiooncology arises, rationale closer connect laminopathy radioprotection research.

Language: Английский

Citations

0
Recent advances in regulating the cell cycle through inhibiting CDKs for cancer treatment DOI

Weijiao Chen,

Xujie Zhuang, Yuanyuan Chen

et al.

Chinese Journal of Natural Medicines, Journal Year: 2025, Volume and Issue: 23(3), P. 286 - 298

Published: March 1, 2025

Language: Английский

Citations

0
Strategies for the Viral Exploitation of Nuclear Pore Transport Pathways DOI Creative Commons
Xin Zhang, Keesiang Lim,

Yujia Qiu

et al.

Viruses, Journal Year: 2025, Volume and Issue: 17(2), P. 151 - 151

Published: Jan. 23, 2025

Viruses frequently exploit the host’s nucleocytoplasmic trafficking machinery to facilitate their replication and evade immune defenses. By encoding specialized proteins other components, they strategically target host nuclear transport receptors (NTRs) nucleoporins within spiderweb-like inner channel of pore complex (NPC), enabling efficient access nucleus. This review explores intricate mechanisms governing import export viral with a focus on interplay between factors determinants that are essential for these processes. Given pivotal role shuttling in life cycle, we also examine therapeutic strategies aimed at disrupting pathways. includes evaluating efficacy pharmacological inhibitors impairing assessing potential as antiviral treatments. Furthermore, emphasize need continued research develop targeted therapies leverage vulnerabilities trafficking. Emerging high-resolution techniques, such advanced imaging computational modeling, transforming our understanding dynamic interactions viruses NPC. These cutting-edge tools driving progress identifying novel opportunities uncovering deeper insights into pathogenesis. highlights importance advancements paving way innovative strategies.

Language: Английский

Citations

0
Mechanical Forces, Nucleus, Chromosomes, and Chromatin DOI Creative Commons
M. Kloc, J. Wosik

Biomolecules, Journal Year: 2025, Volume and Issue: 15(3), P. 354 - 354

Published: March 1, 2025

Individual cells and within the tissues organs constantly face mechanical challenges, such as tension, compression, strain, shear stress, rigidity of cellular extracellular surroundings. Besides external forces, their components are also subjected to intracellular pulling, pushing, stretching, created by sophisticated force-generation machinery cytoskeleton molecular motors. All these stressors switch on mechanotransduction pathways, allowing respond adapt. Mechanical force-induced changes at cell membrane transmitted nucleus its nucleoskeleton, affecting nucleocytoplasmic transport, chromatin conformation, transcriptional activity, replication, genome, which, in turn, orchestrate behavior. The memory mechanoresponses is stored epigenetic structure modifications. state response acellular environment determines identity, fate, immune invading pathogens. Here, we give a short overview latest developments understanding processes, emphasizing effects nuclei, chromosomes, chromatin.

Language: Английский

Citations

0
Mechanical remodeling of nuclear biomolecular condensates DOI
Giulia Soggia, Yasmin ElMaghloob,

Annie-Kermen Boromangnaeva

et al.

Physiology, Journal Year: 2024, Volume and Issue: 40(1), P. 000 - 000

Published: Aug. 7, 2024

Organism health relies on cell proliferation, migration, and differentiation. These universal processes depend cytoplasmic reorganization driven notably by the cytoskeleton its force-generating motors. Their activity generates forces that mechanically agitate nucleus interior. New evidence from reproductive biology revealed these cytoskeletal can be tuned to remodel nuclear membraneless compartments, known as biomolecular condensates, regulate their RNA processing function for success of subsequent division is critical fertility. Both condensate are common numerous physiological pathological contexts, raising possibility mechanical remodeling condensates may a much broader mechanism regulating function. Here, we review this newfound venture into contexts disease where it relevant, with focus reproduction, cancer, premature aging.

Language: Английский

Citations

1
Interdependence between Nuclear Pore Gatekeepers and Genome Caretakers: Cues from Genome Instability Syndromes DOI Open Access
Lidia Larizza, Elisa Adele Colombo

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(17), P. 9387 - 9387

Published: Aug. 29, 2024

This review starts off with the first germline homozygous variants of Nucleoporin 98 gene (NUP98) in siblings whose clinical presentation recalls Rothmund–Thomson (RTS) and Werner (WS) syndromes. The progeroid phenotype caused by a associated haematological malignancies neurodegenerative disorders primed search for interplay between caretakers involved genome instability syndromes Nuclear Pore Complex (NPC) components. In context basic information on NPC architecture functions, we discuss studies interdependence gatekeepers WS Hereditary Fibrosing Poikiloderma (POIKTMP), both entering differential diagnosis RTS. WS, WRN/WRNIP complex interacts nucleoporins Y-complex NDC1 altering architecture. POIKTMP, mutated FAM111B, recruited Y-complex’s SEC13 NUP96, several Nups safeguarding structure. linkage defective to highlights attempt activate repair hub at nuclear periphery restore DNA damage. two separate POIKTMP are drawn close interaction their damage sensors shared hallmark short fragile telomeres disclosing major role telomere maintenance.

Language: Английский

Citations

1