3D-Q-FISH/Telomere/TRF2 Nanotechnology Identifies a Progressively Disturbed Telomere/Shelterin/Lamin AC Complex as the Common Pathogenic, Molecular/Spatial Denominator of Classical Hodgkin Lymphoma DOI Creative Commons
Hans Knecht, Tina Petrogiannis‐Haliotis,

Sherif Louis

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(21), P. 1748 - 1748

Published: Oct. 23, 2024

The bi- or multinucleated Reed-Sternberg cell (RS) is the diagnostic cornerstone of Epstein-Barr Virus (EBV)-positive and EBV-negative classical Hodgkin lymphoma (cHL). cHL a germinal center (GC)-derived B-cell disease. cells (H) are mononuclear precursors RS. An experimental model has to fulfill three conditions qualify as common pathogenic denominator: (i) be GC-derived origin, (ii) avoid EBV latency III expression (iii) support permanent EBV-encoded oncogenic latent membrane protein (LMP1) upon induction. These unified in EBV-, diffuse large B-Cell (DLBCL) line BJAB-tTA-LMP1. 3D reconstructive nanotechnology revealed spatial, quantitative qualitative disturbance telomere/shelterin interactions H-like cells, with further progression during transition RS-like including progressive complexity karyotype every mitotic cycle, due BBF (breakage/bridge/fusion) events. findings this were confirmed patient samples correlate clinical outcomes. Moreover, vitro, significant lamin AC/telomere interaction progressively occurred. In summary, our research over past decades identified first lymphoid malignancy driven by disturbed telomere/shelterin/lamin AC interaction, generating Our may act trailblazer for tailored therapies refractory cHL.

Language: Английский

Behind the stoNE wall: a fervent activity for nuclear lipids DOI Creative Commons

Kseniya Samardak,

Janélie Bâcle,

María Moriel‐Carretero

et al.

Biochimie, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 1, 2024

Language: Английский

Citations

5
Astragalus polysaccharide alleviates benzene-induced DNA damage and hematopoietic toxicity by inhibiting oxidative stress DOI

Jinxiu Feng,

Xulei Zuo,

Xingxing Gao

et al.

Food Bioscience, Journal Year: 2025, Volume and Issue: unknown, P. 106593 - 106593

Published: April 1, 2025

Language: Английский

Citations

0
TRF2–RAP1 represses RAD51-dependent homology-directed telomere repair by promoting BLM-mediated D-loop unwinding and inhibiting BLM–DNA2-dependent 5′-end resection DOI Creative Commons

Fengshan Liang,

Rekha Rai,

Tori Sodeinde

et al.

Nucleic Acids Research, Journal Year: 2024, Volume and Issue: 52(16), P. 9695 - 9709

Published: July 31, 2024

Abstract Inappropriate homology-directed repair (HDR) of telomeres results in catastrophic telomere loss and aberrant chromosome fusions, leading to genome instability. We have previously shown that the TRF2–RAP1 heterodimer protects from engaging HDR. Cells lacking basic domain TRF2 functional RAP1 display HDR-mediated clustering, resulting formation ultrabright (UTs) massive fusions. Using purified proteins, we uncover three distinct molecular pathways utilizes protect show mechanistically inhibits RAD51-initiated telomeric D-loop formation. Both RAP1-binding are required block RAD51-mediated homology search. recruits BLM helicase through its TRFH promote BLM-mediated unwinding D-loops. In addition, BLM–DNA2-mediated 5′ end resection, preventing generation 3′ single-stranded overhangs necessary for RAD51-dependent Importantly, cells expressing mutants unable interact with accumulate D-loops UTs. Our findings mechanisms coordinated by

Language: Английский

Citations

3
Acclimation during Embryogenesis Remodulates Telomerase Activity and Gene Expression in Baikal Whitefish Larvae, Mitigating the Effects of Acute Temperature Stress DOI Creative Commons

А. Г. Королева,

Eugenia A. Vakhteeva,

Alexander A. Epifantsev

et al.

Animals, Journal Year: 2024, Volume and Issue: 14(19), P. 2839 - 2839

Published: Oct. 2, 2024

Acclimation through the hormesis effect increases plasticity of organisms, which has been shown for many ectothermic animals, including fish. We investigated temperature acclimation in Baikal whitefish Coregonus baicalensis (Dybowski, 1874). Telomere length, telomerase activity, and expression genes, whose products are involved regulation telomere length defense against reactive oxygen species, were selected to assess state larvae. acute stress (+12 °C) had no on but altered activity (acclimation decreased it; increased it) levels genes expression. Under stress, superoxide dismutase was acclimated larvae that glutathione peroxidases non-acclimated larvae, may indicate lower species formation slower antioxidant responses The some telomere-related reduced under tzap smg improve control by preventing them from lengthening or shortening, individuals. data obtained a positive remodulation their transcriptional profile.

Language: Английский

Citations

2
3D-Q-FISH/TRF2 Nanotechnology Identifies a Progressively Disturbed Telomere/ Shelterin/Lamin AC Complex as the Common Pathogenic, Molecular/Spatial Denominator of Classical Hodgkin Lymphoma DOI Open Access
Hans Knecht,

Photini Petrogiannis-Haliotis,

Sherif Louis

et al.

Published: Aug. 6, 2024

The bi- or multi-nucleated Reed-Sternberg cell (RS) is the diagnostic cornerstone of EBV-positive and EBV-negative classical Hodgkin lymphoma (cHL). cHL a germinal center (GC) derived B-cell disease. cells (H) are mononuclear precursors RS. An experimental model has to fulfill three conditions qualify as common pathogenic denominator: i) be center-derived origin, ii) avoid EBV latency III expression, iii) support permanent LMP1 expression upon induction. These unified in EBV-, Diffuse Large B-Cell Lymphoma (DLBCL) line BJAB-tTA-LMP1. 3D reconstuctive nanotechnology revealed spatial, quantititive qualitative disturbance telomere/shelterin interactions H-like cells, further progression during transition RS-like including progressive complexity karytotype with every mitotic cycle, due BBF (breakage/bridge/fusion) events. findings this were confirmed on patient samples correlate clincal outcome. Moreover, vitro signficant lamin AC/telomere interaction progressively occured. In summary, our research over past decades identifed first lymphoid maligancy driven by disturbed telomere/shelterin/lamin AC interaction, generating Our may act trailblazer for tailored therapies refractory cHL.

Language: Английский

Citations

1
3D-Q-FISH/Telomere/TRF2 Nanotechnology Identifies a Progressively Disturbed Telomere/Shelterin/Lamin AC Complex as the Common Pathogenic, Molecular/Spatial Denominator of Classical Hodgkin Lymphoma DOI Creative Commons
Hans Knecht, Tina Petrogiannis‐Haliotis,

Sherif Louis

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(21), P. 1748 - 1748

Published: Oct. 23, 2024

The bi- or multinucleated Reed-Sternberg cell (RS) is the diagnostic cornerstone of Epstein-Barr Virus (EBV)-positive and EBV-negative classical Hodgkin lymphoma (cHL). cHL a germinal center (GC)-derived B-cell disease. cells (H) are mononuclear precursors RS. An experimental model has to fulfill three conditions qualify as common pathogenic denominator: (i) be GC-derived origin, (ii) avoid EBV latency III expression (iii) support permanent EBV-encoded oncogenic latent membrane protein (LMP1) upon induction. These unified in EBV-, diffuse large B-Cell (DLBCL) line BJAB-tTA-LMP1. 3D reconstructive nanotechnology revealed spatial, quantitative qualitative disturbance telomere/shelterin interactions H-like cells, with further progression during transition RS-like including progressive complexity karyotype every mitotic cycle, due BBF (breakage/bridge/fusion) events. findings this were confirmed patient samples correlate clinical outcomes. Moreover, vitro, significant lamin AC/telomere interaction progressively occurred. In summary, our research over past decades identified first lymphoid malignancy driven by disturbed telomere/shelterin/lamin AC interaction, generating Our may act trailblazer for tailored therapies refractory cHL.

Language: Английский

Citations

0