RPS15 Coordinates with CtIP to Facilitate Homologous Recombination and Confer Therapeutic Resistance in Breast Cancer DOI

Baohang Lin,

Guan Huang,

Zishan Yuan

и другие.

Radiation Research, Год журнала: 2024, Номер 202(5)

Опубликована: Окт. 3, 2024

The repair of DNA double-strand breaks (DSBs) through homologous recombination (HR) is vital for maintaining the stability and integrity genome. RNA binding proteins (RBPs) intricately regulate damage process, yet precise molecular mechanisms underlying their function remain incompletely understood. In this study, we highlight pivotal role RPS15, a representative RBP, in repair. Specifically, demonstrate that RPS15 promotes end resection, crucial step recombination. Notably, identify an interaction between CtIP, key factor This essential CtIP recruitment to DSB sites, subsequent RPA coating, RAD51 replacement, all critical steps efficient conferring resistance genotoxic treatments. Functionally, suppressing expression sensitizes cancer cells X-ray radiation enhances therapeutic synergistic effect PARP1 inhibitors breast cells. summary, our findings reveal resection ensure effective repair, suggesting its potential as target treatment.

Язык: Английский

ARID1A suppresses R-loop-mediated STING-type I interferon pathway activation of anti-tumor immunity DOI

Matthew B. Maxwell,

Marianne S. Hom, Jawoon Yi

и другие.

Cell, Год журнала: 2024, Номер 187(13), С. 3390 - 3408.e19

Опубликована: Май 15, 2024

Язык: Английский

Процитировано

30

RNA biogenesis and RNA metabolism factors as R-loop suppressors: a hidden role in genome integrity DOI Open Access
Rosa Luna, Belén Gómez‐González, Andrés Aguilera

и другие.

Genes & Development, Год журнала: 2024, Номер unknown

Опубликована: Июль 10, 2024

Genome integrity relies on the accuracy of DNA metabolism, but as appreciated for more than four decades, transcription enhances mutation and recombination frequencies. More recent research provided evidence a previously unforeseen link between RNA which is often related to accumulation DNA–RNA hybrids R-loops. In addition physiological roles, R-loops interfere with replication repair, providing molecular scenario origin genome instability. Here, we review current knowledge multiple factors that prevent or resolve consequent transcription–replication conflicts thus act modulators dynamics.

Язык: Английский

Процитировано

6

Arid5a uses disordered extensions of its core ARID domain for distinct DNA- and RNA-recognition and gene regulation DOI Creative Commons
Julian von Ehr,

Lasse Oberstrass,

Ege Yazgan

и другие.

Journal of Biological Chemistry, Год журнала: 2024, Номер 300(7), С. 107457 - 107457

Опубликована: Июнь 12, 2024

Язык: Английский

Процитировано

5

Epitranscriptome in action: RNA modifications in the DNA damage response DOI Creative Commons
Blerta Xhemalçe, Kyle M. Miller, Natalia Gromak

и другие.

Molecular Cell, Год журнала: 2024, Номер 84(19), С. 3610 - 3626

Опубликована: Окт. 1, 2024

Язык: Английский

Процитировано

5

Chromatin remodeling and spatial concerns in DNA double-strand break repair DOI Creative Commons
Jessica A. Downs, Susan M. Gasser

Current Opinion in Cell Biology, Год журнала: 2024, Номер 90, С. 102405 - 102405

Опубликована: Июль 30, 2024

The substrate for the repair of DNA damage in living cells is not but chromatin. Chromatin bears a range modifications, which turn bind ligands that compact or open chromatin structure, and determine its spatial organization within nucleus. In some cases, RNA form RNA:DNA hybrids R-loops modulates accessibility. Each these parameters can favor particular pathways repair. nucleosome remodelers are key regulators number remodeling complexes implicated We cover novel insights into impact nuclear organization, R-loop formation, actin, double-strand break repair, focusing on factors alter functional upon ablation.

Язык: Английский

Процитировано

4

Chromatin lysine acylation: On the path to chromatin homeostasis and genome integrity DOI Creative Commons
Feng Chen,

Xingkai He,

Wenchao Xu

и другие.

Cancer Science, Год журнала: 2024, Номер 115(11), С. 3506 - 3519

Опубликована: Авг. 18, 2024

Abstract The fundamental role of cells in safeguarding the genome's integrity against DNA double‐strand breaks (DSBs) is crucial for maintaining chromatin homeostasis and overall genomic stability. Aberrant responses to damage, known as damage (DDRs), can result instability contribute significantly tumorigenesis. Unraveling intricate mechanisms underlying DDRs following severe holds key identify therapeutic targets cancer. Chromatin lysine acylation, encompassing diverse modifications such acetylation, lactylation, crotonylation, succinylation, malonylation, glutarylation, propionylation, butyrylation, has been extensively studied context homeostasis. Here, we delve into modifying enzymes pivotal roles acylation their crosstalk genome response DDRs. Moreover, offer a comprehensive perspective overview latest insights, driven primarily by modification associated regulators.

Язык: Английский

Процитировано

4

METTL Family in Healthy and Disease DOI Creative Commons

Jiejie He,

Fengchen Hao,

Shiqi Song

и другие.

Molecular Biomedicine, Год журнала: 2024, Номер 5(1)

Опубликована: Авг. 19, 2024

Abstract Transcription, RNA splicing, translation, and post-translational protein modification are fundamental processes of gene expression. Epigenetic modifications, such as DNA methylation, play a crucial role in regulating The methyltransferase-like (METTL) family, constituent the 7-β-strand (7BS) methyltransferase subfamily, is broadly distributed across cell nucleus, cytoplasm, mitochondria. Members METTL through their S-adenosyl methionine (SAM) binding domain, can transfer methyl groups to DNA, RNA, or proteins, thereby impacting replication, transcription, mRNA participate maintenance normal function promote disease development. This review primarily examines involvement family differentiation, mitochondrial function, its association with tumor formation, nervous system, cardiovascular diseases. Notably, intricately linked cellular particularly regulation translation factors. represent important molecules development associated patient immunity tolerance radiotherapy chemotherapy. Moreover, future research directions could include drugs antibodies targeting structural domains, utilizing nanomaterials carry miRNA corresponding mRNA. Additionally, precise mechanisms underlying interactions between factors remain be clarified.

Язык: Английский

Процитировано

4

Advancements and Challenges of R-loops in Cancers: Biological Insights and Future Directions DOI
Dengxiong Li, Fanglin Shao, Xinrui Li

и другие.

Cancer Letters, Год журнала: 2024, Номер 610, С. 217359 - 217359

Опубликована: Ноя. 27, 2024

Язык: Английский

Процитировано

4

Mechanisms underlining R-loop biology and implications for human disease DOI Creative Commons
Junzhe Liu,

Fengze Li,

Yulong Cao

и другие.

Frontiers in Cell and Developmental Biology, Год журнала: 2025, Номер 13

Опубликована: Фев. 21, 2025

R-loops are three-stranded non-canonical nucleic acid structures composed of nascent RNA hybridized with the template DNA strand, leaving non-template strand displaced. These play crucial roles in regulating gene expression, replication, and transcription processes. However, have also been increasingly described as highly deleterious, causing genomic instability damage. To maintain at a relatively safe level, complex regulatory mechanisms exist to prevent their excessive formation. The growing understanding R-loop functions has provided valuable insights into structure potential clinical applications. Emerging research indicates that contribute pathogenesis various disorders, including neurodegenerative, immune-related, neoplastic diseases. This review summarizes metabolism its significance etiology associated disorders. By elucidating governing R-loops, we aim establish theoretical foundation for disease exploring novel therapeutic strategies targeting these hybrid structures.

Язык: Английский

Процитировано

0

R-loop homeostasis in genome dynamics, gene expression and development DOI
Paula Aguilera, Andrés Aguilera

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

Опубликована: Март 4, 2025

Язык: Английский

Процитировано

0