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R-Loops and R-Loop-Binding Proteins in Cancer Progression and Drug Resistance

R-loops are three-stranded DNA/RNA hybrids that form by the annealing of the mRNA transcript to its coding template while displacing the non-coding strand. While R-loop formation regulates physiological genomic and mitochondrial transcription and DNA damage response, imbalanced R-loop formation can...

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Autores principales: Elsakrmy, Noha, Cui, Haissi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10138518/
https://www.ncbi.nlm.nih.gov/pubmed/37108225
http://dx.doi.org/10.3390/ijms24087064
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author Elsakrmy, Noha
Cui, Haissi
author_facet Elsakrmy, Noha
Cui, Haissi
author_sort Elsakrmy, Noha
collection PubMed
description R-loops are three-stranded DNA/RNA hybrids that form by the annealing of the mRNA transcript to its coding template while displacing the non-coding strand. While R-loop formation regulates physiological genomic and mitochondrial transcription and DNA damage response, imbalanced R-loop formation can be a threat to the genomic integrity of the cell. As such, R-loop formation is a double-edged sword in cancer progression, and perturbed R-loop homeostasis is observed across various malignancies. Here, we discuss the interplay between R-loops and tumor suppressors and oncogenes, with a focus on BRCA1/2 and ATR. R-loop imbalances contribute to cancer propagation and the development of chemotherapy drug resistance. We explore how R-loop formation can cause cancer cell death in response to chemotherapeutics and be used to circumvent drug resistance. As R-loop formation is tightly linked to mRNA transcription, their formation is unavoidable in cancer cells and can thus be explored in novel cancer therapeutics.
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spelling pubmed-101385182023-04-28 R-Loops and R-Loop-Binding Proteins in Cancer Progression and Drug Resistance Elsakrmy, Noha Cui, Haissi Int J Mol Sci Review R-loops are three-stranded DNA/RNA hybrids that form by the annealing of the mRNA transcript to its coding template while displacing the non-coding strand. While R-loop formation regulates physiological genomic and mitochondrial transcription and DNA damage response, imbalanced R-loop formation can be a threat to the genomic integrity of the cell. As such, R-loop formation is a double-edged sword in cancer progression, and perturbed R-loop homeostasis is observed across various malignancies. Here, we discuss the interplay between R-loops and tumor suppressors and oncogenes, with a focus on BRCA1/2 and ATR. R-loop imbalances contribute to cancer propagation and the development of chemotherapy drug resistance. We explore how R-loop formation can cause cancer cell death in response to chemotherapeutics and be used to circumvent drug resistance. As R-loop formation is tightly linked to mRNA transcription, their formation is unavoidable in cancer cells and can thus be explored in novel cancer therapeutics. MDPI 2023-04-11 /pmc/articles/PMC10138518/ /pubmed/37108225 http://dx.doi.org/10.3390/ijms24087064 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Elsakrmy, Noha
Cui, Haissi
R-Loops and R-Loop-Binding Proteins in Cancer Progression and Drug Resistance
title R-Loops and R-Loop-Binding Proteins in Cancer Progression and Drug Resistance
title_full R-Loops and R-Loop-Binding Proteins in Cancer Progression and Drug Resistance
title_fullStr R-Loops and R-Loop-Binding Proteins in Cancer Progression and Drug Resistance
title_full_unstemmed R-Loops and R-Loop-Binding Proteins in Cancer Progression and Drug Resistance
title_short R-Loops and R-Loop-Binding Proteins in Cancer Progression and Drug Resistance
title_sort r-loops and r-loop-binding proteins in cancer progression and drug resistance
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10138518/
https://www.ncbi.nlm.nih.gov/pubmed/37108225
http://dx.doi.org/10.3390/ijms24087064
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