RTEL1 is upregulated in gastric cancer and promotes tumor growth DOI Creative Commons
Chunyu Yang,

Suzeng Wang,

Ge Gao

и другие.

Journal of Cancer Research and Clinical Oncology, Год журнала: 2024, Номер 151(1)

Опубликована: Дек. 26, 2024

Gastric cancer (GC) is one of the most common cancers worldwide, with increasing incidence and mortality rates. It typically diagnosed at advanced stages, leading to a poor prognosis. GC highly heterogeneous disease its progression associated complex interplay between genetic environmental factors. Identifying novel genes pathways involved in development crucial for improving therapeutic outcome. Regulator Telomerase Length 1 (RTEL1) has been found maintain telomere stability through helicase activity, facilitating reconstruction repair. However, precise role RTEL1 human cancers, particularly GC, not yet fully understood. In this study, we observed significantly increased expression tissues, which was Functionally, promotes cell proliferation both vitro vivo. Additionally, appears regulate multiple signaling pathways, particular promoting effect on cycle progression. Notably, CDC23 TRIP13 are potential downstream target RTEL1, may mediate tumor-promoting effects GC. These findings suggest that plays critical tumorigenesis could be promising therapy prognosis

Язык: Английский

Why cells need iron: a compendium of iron utilisation DOI Creative Commons
Megan R. Teh, Andrew E. Armitage, Hal Drakesmith

и другие.

Trends in Endocrinology and Metabolism, Год журнала: 2024, Номер unknown

Опубликована: Май 1, 2024

Iron deficiency is globally prevalent, causing an array of developmental, haematological, immunological, neurological, and cardiometabolic impairments, associated with symptoms ranging from chronic fatigue to hair loss. Within cells, iron utilised in a variety ways by hundreds different proteins. Here, we review links between molecular activities regulated the pathophysiological effects deficiency. We identify specific enzyme groups, biochemical pathways, cellular functions, cell lineages that are particularly dependent. provide examples how deprivation influences multiple key systems tissues, including immunity, hormone synthesis, cholesterol metabolism. propose greater mechanistic understanding physiological processes may lead new therapeutic opportunities across range diseases.

Язык: Английский

Процитировано

12
Knockdown of RTEL1 Alleviates Chronic Obstructive Pulmonary Disease by Modulating M1, M2 Macrophage Polarization and Inflammation DOI Creative Commons
Heping Xu,

Huan Niu,

Hong Wang

и другие.

COPD Journal of Chronic Obstructive Pulmonary Disease, Год журнала: 2024, Номер 21(1)

Опубликована: Фев. 29, 2024

Chronic obstructive pulmonary disease (COPD) is a common chronic characterized by airflow obstruction, which seriously threatens people's health. The COPD mouse model was established with cigarette smoke induction. Hematoxylin-eosin staining and Masson were carried out to observe the pathological changes of lung tissues in mice. RTEL1 silenced mice, immunohistochemistry used detect RTEL1, ki67 Caspase-3 expression. role inflammation evaluated ELISA, impacts on M1 M2 macrophage markers (iNOS CD206) qPCR western blotting. In model, there an increase number inflammatory cells, slightly disorganized cell arrangement, unclear hierarchy, condensed solidified nuclei, while knockdown improved infiltration. Moreover, reduced ki67-positive cells increased positive group. factors (IL-1β, MMP-9, TNF-α, IL-4, IL-6, IL-23) suppressed iNOS raised CD206 inhibited. conclusion, promoted inhibited polarization alleviate COPD.

Язык: Английский

Процитировано

6
High-throughput characterization of functional variants highlights heterogeneity and polygenicity underlying lung cancer susceptibility DOI Creative Commons
Erping Long, Harsh Patel,

Alyxandra Golden

и другие.

The American Journal of Human Genetics, Год журнала: 2024, Номер 111(7), С. 1405 - 1419

Опубликована: Июнь 20, 2024

Язык: Английский

Процитировано

4
Telomeropathies in Interstitial Lung Disease and Lung Transplant Recipients DOI Open Access
Brian D. Southern,

Shruti Gadre

Journal of Clinical Medicine, Год журнала: 2025, Номер 14(5), С. 1496 - 1496

Опубликована: Фев. 24, 2025

Telomeropathies, or telomere biology disorders (TBDs), are syndromes that can cause a number of medical conditions, including interstitial lung disease (ILD), bone marrow failure, liver fibrosis, and other diseases. They occur due to genetic mutations the telomerase complex enzymes result in premature shortening telomeres, caps on ends cellular DNA protect chromosome length during cell division, leading early senescence death. Idiopathic pulmonary fibrosis (IPF) is most common manifestation disorders, although it has been described diseases as well, such rheumatoid arthritis-associated ILD chronic hypersensitivity pneumonitis. Telomere-related be inherited sporadically. Identifying these patients offering counseling important because telomerapathies have associated with poorer outcomes death, transplantation, hospitalization, FVC decline. Additionally, treatment immunosuppressants shown worse outcomes. Currently, there no specific for TBD except transplant organ failing, promising strategies currently under investigation. Shortened routinely discovered undergoing transplantation IPF. Testing detect suggestive signs symptoms allow more comprehensive multidisciplinary care pre- post-transplant. Patients reported both extrapulmonary complications at higher frequency than recipients, graft-specific complications, increased infections, related immunosuppressive therapy.

Язык: Английский

Процитировано

0
Rapid dynamics allow the low-abundance RTEL1 helicase to promote telomere replication DOI Creative Commons
Guanhui Wu,

Erin Taylor,

Daniel T. Youmans

и другие.

Nucleic Acids Research, Год журнала: 2025, Номер 53(5)

Опубликована: Фев. 27, 2025

Abstract Regulator of telomere length 1 (RTEL1) helicase facilitates replication by disassembling DNA secondary structures, such as G-quadruplexes and telomeric loops (t-loops), at the ends chromosomes. The recruitment RTEL1 to telomeres occurs during S-phase cell cycle, but dynamics process has not been studied. Here, we utilized CRISPR genome editing single-molecule imaging monitor movement within human nuclei. utilizes rapid three-dimensional diffusion search for other nuclear targets. Only 5% chromatin-bound is associated with any time in S-phase, telomere-bound much more extended associations. This binding enhanced interaction between protein TRF2 largely independent ATPase activity. absence catalytic activity leads severe defects proliferation, slow progression out chromosome end-to-end fusion events. We propose that allows this low-abundance explore nucleus, bind TRF2, be recruited telomeres.

Язык: Английский

Процитировано

0
CMG helicase disassembly is essential and driven by two pathways in budding yeast DOI Creative Commons
Cristian Polo Rivera, Tom Deegan, Karim Labib

и другие.

The EMBO Journal, Год журнала: 2024, Номер unknown

Опубликована: Июль 22, 2024

Язык: Английский

Процитировано

3
Maternal age is related to offspring DNA methylation: A meta‐analysis of results from the PACE consortium DOI Creative Commons
Edwina Yeung, Richard J. Biedrzycki,

Laura C. Gómez Herrera

и другие.

Aging Cell, Год журнала: 2024, Номер 23(8)

Опубликована: Май 29, 2024

Abstract Worldwide trends to delay childbearing have increased parental ages at birth. Older age may harm offspring health, but mechanisms remain unclear. Alterations in DNA methylation (DNAm) patterns could play a role as aging has been associated with changes gametes of older individuals. We meta‐analyzed epigenome‐wide associations blood DNAm over 9500 newborns and 2000 children (5–10 years old) from the Pregnancy Childhood Epigenetics consortium. In newborns, we identified 33 CpG sites 13 loci maternal (P FDR < 0.05). Eight these CpGs were located near/in MTNR1B gene, coding for melatonin receptor. Regional analysis them together differentially methylated region consisting 9 in/near , which higher was greater = 6.92 × 10 −8 ) newborns. childhood samples, differences nominally significant ( p 0.05) retained same positive direction, suggesting persistence associations. Maternal also positively three RTEL1‐TNFRSF6B birth 0.0001). Of remaining persistent childhood, cg26709300 YPEL3/BOLA2B external data expression ITGAL an immune regulator. While further study is needed establish causality, particularly due small effect sizes observed, our results potentially support mechanism underlying child health.

Язык: Английский

Процитировано

2
Telomere function and regulation from mouse models to human ageing and disease DOI
Corey Winston Jones-Weinert, Laura Mainz, Jan Karlseder

и другие.

Nature Reviews Molecular Cell Biology, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 29, 2024

Язык: Английский

Процитировано

2
Separation of telomere protection from length regulation by two different point mutations at amino acid 492 of RTEL1 DOI Open Access
Riham Smoom,

Catherine Lee May,

Dan Lichtental

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Фев. 29, 2024

RTEL1 is an essential DNA helicase that plays multiple roles in genome stability and telomere length regulation. A variant of with a lysine at position 492 associated short telomeres

Язык: Английский

Процитировано

1
The Response of the Replication Apparatus to Leading Template Strand Blocks DOI Creative Commons
Marina A. Bellani,

Althaf Shaik,

Ishani Majumdar

и другие.

Cells, Год журнала: 2023, Номер 12(22), С. 2607 - 2607

Опубликована: Ноя. 11, 2023

Duplication of the genome requires replication apparatus to overcome a variety impediments, including covalent DNA adducts, most challenging which is on leading template strand. Replisomes consist two functional units, helicase unwind and polymerases synthesize it. The multi-protein complex that encircles strand makes first contact with adduct. size channel in would appear preclude transit by large adducts such as DNA: protein complexes (DPC). Here we discuss some extensively studied pathways support restart after replisome encounters adducts. We also call attention recent work highlights tolerance for ostensibly too pass through central channel.

Язык: Английский

Процитировано

2