R-loops in neurodegeneration DOI Creative Commons
Chiara Beghè,

Helena Harpham,

Yasmine Barberic

et al.

Current Opinion in Genetics & Development, Journal Year: 2025, Volume and Issue: 92, P. 102345 - 102345

Published: April 8, 2025

Neurodegenerative diseases are associated with the progressive loss of neurons. R-loops non-canonical nucleic acid structures formed during transcription and composed an RNA/DNA hybrid a displaced single-stranded DNA. Whilst important regulators cellular processes, they also pathologies multiple disorders, including repeat expansion, motor neuron, inflammatory ageing diseases. In this review, we discuss how contribute to pathological mechanisms that underpin neurodegeneration. We highlight role in several hallmarks neurodegenerative RNA DNA defects, damage, protein aggregation, inflammation, mitochondrial dysfunction, neuronal cell death. potential as therapeutic targets for disorders.

Language: Английский

Dynamic R-loops at centromeres ensure chromosome alignment during oocyte meiotic divisions in mice DOI Creative Commons
Yinghong Chen, Liying Wang,

Qiuxing Zhou

et al.

Science Bulletin, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

Citations

0
Senataxin prevents replicative stress induced by the Myc oncogene DOI Creative Commons
Silvia Sberna, M. Filipuzzi,

Nicola Bianchi

et al.

Cell Death and Disease, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 19, 2025

Abstract Replicative stress (RS) is emerging as a promising therapeutic target in oncology, yet full exploitation of its potential requires detailed understanding the mechanisms and genes involved. Here, we investigated RNA helicase Senataxin (SETX), an enzyme that resolves RNA-DNA hybrids R-loops, to address role preventing RS by oncogenic Myc. Upon Myc activation, silencing SETX led selective engagement DNA damage response (DDR) robust cytotoxicity. Pharmacological dissection upstream kinases regulating DDR uncovered protective ATR pathway, once inhibited, boosted driven-DDR. While loss did not lead genome-wide increase mechanistic analyses revealed enhanced R-loops localized at DDR-foci newly replicated genomic loci, compatible with resolving alleviate Myc-induced RS. Genome-wide mapping double-strand breaks confirmed exacerbated transcription-replication conflict (TRC) regions early sites. We propose prevents TRCs transcription-associated encounter replisome. The identification genetic liability opens up new options against aggressive Myc-driven tumors.

Language: Английский

Citations

0
DNA-RNA hybrids in inflammation: sources, immune response, and therapeutic implications DOI
Lingjun Chen, Lei Hu, Chang Han

et al.

Journal of Molecular Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: March 25, 2025

Language: Английский

Citations

0
R-loops in neurodegeneration DOI Creative Commons
Chiara Beghè,

Helena Harpham,

Yasmine Barberic

et al.

Current Opinion in Genetics & Development, Journal Year: 2025, Volume and Issue: 92, P. 102345 - 102345

Published: April 8, 2025

Neurodegenerative diseases are associated with the progressive loss of neurons. R-loops non-canonical nucleic acid structures formed during transcription and composed an RNA/DNA hybrid a displaced single-stranded DNA. Whilst important regulators cellular processes, they also pathologies multiple disorders, including repeat expansion, motor neuron, inflammatory ageing diseases. In this review, we discuss how contribute to pathological mechanisms that underpin neurodegeneration. We highlight role in several hallmarks neurodegenerative RNA DNA defects, damage, protein aggregation, inflammation, mitochondrial dysfunction, neuronal cell death. potential as therapeutic targets for disorders.

Language: Английский

Citations

0