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R-loops: formation, function, and relevance to cell stress

Exposure of genomic, single-stranded DNA (ssDNA) during transcription and replication creates opportunities for the formation of inappropriate secondary structures. Cells manage this exposure by using topoisomerases and helicases to reduce the inherent topological stress that arises from unwinding t...

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Autores principales: Allison, David F, Wang, Gang Greg
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Shared Science Publishers OG 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6551709/
https://www.ncbi.nlm.nih.gov/pubmed/31225499
http://dx.doi.org/10.15698/cst2019.02.175
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author Allison, David F
Wang, Gang Greg
author_facet Allison, David F
Wang, Gang Greg
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description Exposure of genomic, single-stranded DNA (ssDNA) during transcription and replication creates opportunities for the formation of inappropriate secondary structures. Cells manage this exposure by using topoisomerases and helicases to reduce the inherent topological stress that arises from unwinding the double helix and by coating ssDNA with protective protein complexes. Interestingly, specific DNA-RNA hybrids, known as R-loops, form during transcription and exist in homeostasis throughout the genomes of prokaryotes and eukaryotes. These hybrids nucleate from guanine rich clusters in the template strand and extend across GC rich spans of transcribed genes. In vivo regulatory functions have evolved from R-loops, including regulation of gene expression and telomere lengthening. However, they also exist as a form of stress, particularly when replication forks collide with the transcription machinery. New methodologies and models are being developed to delineate the biology of R-loops, including those related to cell stress-based diseases like cancer. As accumulation of R-loops is associated with disease, targeting molecular pathways that regulate their formation or removal could provide new avenues for therapeutic intervention. This review covers recent understandings of the molecular basis for R-loop formation, removal, and biological outcomes in the context of cellular stress.
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spelling pubmed-65517092019-06-20 R-loops: formation, function, and relevance to cell stress Allison, David F Wang, Gang Greg Cell Stress Review Exposure of genomic, single-stranded DNA (ssDNA) during transcription and replication creates opportunities for the formation of inappropriate secondary structures. Cells manage this exposure by using topoisomerases and helicases to reduce the inherent topological stress that arises from unwinding the double helix and by coating ssDNA with protective protein complexes. Interestingly, specific DNA-RNA hybrids, known as R-loops, form during transcription and exist in homeostasis throughout the genomes of prokaryotes and eukaryotes. These hybrids nucleate from guanine rich clusters in the template strand and extend across GC rich spans of transcribed genes. In vivo regulatory functions have evolved from R-loops, including regulation of gene expression and telomere lengthening. However, they also exist as a form of stress, particularly when replication forks collide with the transcription machinery. New methodologies and models are being developed to delineate the biology of R-loops, including those related to cell stress-based diseases like cancer. As accumulation of R-loops is associated with disease, targeting molecular pathways that regulate their formation or removal could provide new avenues for therapeutic intervention. This review covers recent understandings of the molecular basis for R-loop formation, removal, and biological outcomes in the context of cellular stress. Shared Science Publishers OG 2019-01-21 /pmc/articles/PMC6551709/ /pubmed/31225499 http://dx.doi.org/10.15698/cst2019.02.175 Text en Copyright: © 2019 Allison and Wang https://creativecommons.org/licenses/by/4.0/ This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.
spellingShingle Review
Allison, David F
Wang, Gang Greg
R-loops: formation, function, and relevance to cell stress
title R-loops: formation, function, and relevance to cell stress
title_full R-loops: formation, function, and relevance to cell stress
title_fullStr R-loops: formation, function, and relevance to cell stress
title_full_unstemmed R-loops: formation, function, and relevance to cell stress
title_short R-loops: formation, function, and relevance to cell stress
title_sort r-loops: formation, function, and relevance to cell stress
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6551709/
https://www.ncbi.nlm.nih.gov/pubmed/31225499
http://dx.doi.org/10.15698/cst2019.02.175
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