Distinct Mechanisms of Recognition of Phosphorylated RNAPII C-Terminal Domain by BRCT Repeats of the BRCA1-BARD1 Complex: Insights from Structural and Functional Analyses

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 22, 2025

Abstract Transcription competes with other DNA-dependent processes, such as DNA repair, for access to its substrate, DNA. However, the principles governing interplay between these processes remain poorly understood. Evidence suggests that BRCA1-BARD1 complex, a key player in damage response, may act mediator of this crosstalk. In study, we investigated molecular mechanism underpinning interaction RNA polymerase II (RNAPII) and well functional implications. Our findings reveal BRCT repeat BRCA1 binds Ser5-phosphorylated CTD RNAPII, utilising previously established ligands. Furthermore, demonstrate is critical organisation RNAPII into condensates liquid-like properties. Analysis disease-associated variants within repeats further supports biological relevance condensation. Collectively, our results suggest complex coordinate transcription repair by facilitating factories.

Язык: Английский

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R-loop homeostasis in genome dynamics, gene expression and development

Current Opinion in Genetics & Development, Год журнала: 2025, Номер 92, С. 102325 - 102325

Опубликована: Март 4, 2025

Язык: Английский

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Transcription-Coupled Repair and R-Loop Crosstalk in Genome Stability

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(8), С. 3744 - 3744

Опубликована: Апрель 16, 2025

Transcription-coupled repair (TCR) and R-loops are two interrelated processes critical to the maintenance of genome stability during transcription. TCR, a specialized sub-pathway nucleotide excision repair, rapidly removes transcription-blocking lesions from transcribed strand active genes, thereby safeguarding transcription fidelity cellular homeostasis. In contrast, R-loops, RNA–DNA hybrid structures formed co-transcriptionally, play not only regulatory roles in gene expression replication but can also contribute instability when persistently accumulated. Recent experimental evidence has revealed dynamic crosstalk between TCR R-loop resolution pathways. This review highlights current molecular insights into biology, discusses impact their crosstalk, explores emerging therapeutic strategies aimed at optimizing DNA reducing disease risk conditions such as cancer neurodegenerative disorders.

Язык: Английский

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Senataxin Attenuates DNA Damage Response Activation and Suppresses Senescence

Antioxidants, Год журнала: 2024, Номер 13(11), С. 1337 - 1337

Опубликована: Окт. 31, 2024

Oxidative stress, driven by reactive oxygen species (ROS) such as hydrogen peroxide (H

Язык: Английский

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DDX39A resolves replication fork-associated RNA-DNA hybrids to balance fork protection and cleavage for genomic stability maintenance

Molecular Cell, Год журнала: 2024, Номер unknown

Опубликована: Дек. 1, 2024

Язык: Английский

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