Generation of somatic de novo structural variation as a hallmark of cellular senescence in human lung fibroblasts DOI Creative Commons
Valentina Woronzow, Jonas Möhner,

Daniel Remane

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2023, Volume and Issue: 11

Published: Dec. 13, 2023

Cellular senescence is characterized by replication arrest in response to stress stimuli. Senescent cells accumulate aging tissues and can trigger organ-specific possibly systemic dysfunction. Although senescent cell populations are heterogeneous, a key feature that they exhibit epigenetic changes. Epigenetic changes such as loss of repressive constitutive heterochromatin could lead subsequent LINE-1 derepression, phenomenon often described the context or somatic evolution. elements decode retroposition machinery reverse transcription generates cDNA from autonomous non-autonomous TEs potentially reintegrate into genomes cause structural variants. Another cellular mitochondrial dysfunction caused damage. In combination with impaired mitophagy, which characteristic cells, this cytosolic mtDNA accumulation and, genomic consequence, integrations nuclear DNA (nDNA), resulting pseudogenes called

Language: Английский

Z-DNA at the crossroads: untangling its role in genome dynamics DOI

Vinodh J. Sahayasheela,

Mitsuharu Ooga,

Tomotaka Kumagai

et al.

Trends in Biochemical Sciences, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

1
The brain–body energy conservation model of aging DOI
Evan D. Shaulson, Alan A. Cohen, Martin Picard

et al.

Nature Aging, Journal Year: 2024, Volume and Issue: 4(10), P. 1354 - 1371

Published: Oct. 8, 2024

Language: Английский

Citations

7
Primordial Biochemicals Within Coacervate-Like Droplets and the Origins of Life DOI Creative Commons
George B. Stefano, Richard M. Kream

Viruses, Journal Year: 2025, Volume and Issue: 17(2), P. 146 - 146

Published: Jan. 23, 2025

An organism is considered “alive” if it can grow, reproduce, respond to external stimuli, metabolize nutrients, and maintain stability. By this definition, both mitochondria viruses exhibit the key characteristics of independent life. In addition their capacity for self-replication under specifically defined conditions, communicate via shared biochemical elements, alter cellular energy metabolism, adapt local environment. To explain phenomenon, we hypothesize that early viral prototype species evolved from ubiquitous environmental DNA gained within coacervate-like liquid droplets. The high mutation rates experienced in environment streamlined acquisition standard genetic codes adaptation a diverse set host environments. Similarly, mitochondria, eukaryotic intracellular organelles generate resolve oxygen toxicity, originally an infectious bacterial active functionality extracellular space. Thus, while contribute profoundly homeostasis, freestanding existence may lead functional disruptions over time, notably, overproduction reactive species, phenomenon strongly linked aging-related disorders. Overall, more in-depth understanding full extent evolution primordial precursors novel insights therapeutic strategies address neurodegenerative processes promote healthy aging.

Language: Английский

Citations

0
Connecting the dots: Mitochondrial transfer in immunity, inflammation, and cancer DOI Creative Commons
Valentina Artusa,

L De Luca,

Mario Clerici

et al.

Immunology Letters, Journal Year: 2025, Volume and Issue: 274, P. 106992 - 106992

Published: March 6, 2025

Language: Английский

Citations

0
Viruses and Mitochondrial Dysfunction in Neurodegeneration and Cognition: An Evolutionary Perspective DOI Creative Commons
George B. Stefano,

Simon Weissenberger,

Radek Ptáček

et al.

Cellular and Molecular Neurobiology, Journal Year: 2024, Volume and Issue: 44(1)

Published: Oct. 17, 2024

Language: Английский

Citations

3
Yeast EndoG prevents genome instability by degrading extranuclear DNA species DOI Creative Commons
Yang Yu, Xin Wang, Jordan Fox

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Sept. 3, 2024

In metazoans mitochondrial DNA (mtDNA) or retrotransposon cDNA released to cytoplasm are degraded by nucleases prevent sterile inflammation. It remains unknown whether degradation of these also prevents nuclear genome instability. We used an amplicon sequencing-based method in yeast enabling analysis millions DSB repair products. non-dividing stationary phase cells, Pol4-mediated non-homologous end-joining increases, resulting frequent insertions 1–3 nucleotides, and mtDNA (NUMTs) cDNA. Yeast EndoG (Nuc1) nuclease limits insertion transfer very long ( >10 kb) the nucleus, where it forms unstable circles, while promoting formation short NUMTs (~45–200 bp). Nuc1 regulates extranuclear nucleus aging meiosis. propose that preserves stability degrading mtDNA, originate from incompletely mtDNA. This work suggests eliminating preserve stability. Mitochondrial into is this study, authors demonstrate nucleolytic species a model organism their

Language: Английский

Citations

1
Yeast EndoG prevents genome instability by degrading cytoplasmic DNA DOI Creative Commons

Grzegorz Ira,

Yang Yu, Xin Wang

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 5, 2024

Abstract In metazoans release of mitochondrial DNA or retrotransposon cDNA to cytoplasm can cause sterile inflammation and disease 1. Cytoplasmic nucleases degrade these species limit 2,3. It remains unknown whether degradation also prevents nuclear genome instability. To address this question, we decided identify the nuclease regulating transfer cytoplasmic nucleus. We used an amplicon sequencing-based method in yeast enabling analysis millions DSB repair products. Nuclear mtDNA (NUMTs) insertions increase dramatically nondividing stationary phase cells. Yeast EndoG (Nuc1) limits very long (>10 kb) that forms unstable circles rarely insert genome, but it promotes formation short NUMTs (~45-200 bp). Nuc1 regulates nucleus aging during meiosis. propose preserves stability by degrading mtDNA, while originate from incompletely degraded mtDNA. This work suggests eliminating play a role preserving stability.

Language: Английский

Citations

0
A somatic view of the genomic impact of mitochondrial endosymbiosis DOI Creative Commons

Rose M. Doss,

Martin W. Breuss

PLoS Biology, Journal Year: 2024, Volume and Issue: 22(8), P. e3002756 - e3002756

Published: Aug. 23, 2024

The endosymbiosis of mitochondrial ancestors resulted in the transfer genetic material on an evolutionary scale for eukaryotic species. A new study PLOS Biology expands this to genome somatic cells within individuals and highlights its correlation with aging disease.

Language: Английский

Citations

0
Characterization of Nuclear Mitochondrial Insertions in Canine Genome Assemblies DOI Open Access
Peter Z. Schall, Jennifer R. S. Meadows, Fabian Ramos‐Almodovar

et al.

Genes, Journal Year: 2024, Volume and Issue: 15(10), P. 1318 - 1318

Published: Oct. 14, 2024

The presence of mitochondrial sequences in the nuclear genome (Numts) confounds analyses sequence variation, and is a potential source false positives disease studies. To improve analysis variation canines, we completed systematic assessment Numt content across assemblies, canine populations carnivore lineage.

Language: Английский

Citations

0
A personalized multi-platform assessment of somatic mosaicism in the human frontal cortex DOI Creative Commons
Weichen Zhou, Camille Mumm, Yanming Gan

et al.

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

Published: Dec. 21, 2024

Somatic mutations in individual cells lead to genomic mosaicism, contributing the intricate regulatory landscape of genetic disorders and cancers. To evaluate refine detection somatic mosaicism across different technologies with personalized donor-specific assembly (DSA), we obtained tissue from dorsolateral prefrontal cortex (DLPFC) a post-mortem neurotypical 31-year-old individual. We sequenced bulk DLPFC using Oxford Nanopore Technologies (~60X), NovaSeq (~30X), linked-read sequencing (~28X). Additionally, applied Cas9 capture methodology coupled long-read (TEnCATS), targeting active transposable elements. also isolated amplified DNA flow-sorted single neurons MALBAC, 115 these MALBAC libraries on 94 NovaSeq. constructed haplotype-resolved total length 5.77 Gb phase block 2.67 Mb (N50) facilitate cross-platform analysis variations. observed an increase phasing rate 11.6% 38.0% between short-read technologies. By generating catalog phased germline SNVs, CNVs, TEs assembled genome, standard approaches recall variants achieved aggregated rates 97.3% 99.4% based data, setting upper bound for limits. Moreover, utilizing haplotype-based DSA, remarkable reduction false positive calls tissue, ranging 14.9% 72.4%. developed pipelines leveraging DSA information enhance large variant calling cells. examining variation long-reads neurons, identified 468 candidate heterozygous deletions (1.5Mb - 20Mb), 137 which intersected single-cell data. 61 putative (60 Alus, one LINE-1) Collectively, our spans calling, providing comprehensive ab initio ad finem approach resource real human tissue.

Language: Английский

Citations

0