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Replication and transcription on a collision course: eukaryotic regulation mechanisms and implications for DNA stability

DNA replication and transcription are vital cellular processes during which the genetic information is copied into complementary DNA and RNA molecules. Highly complex machineries required for DNA and RNA synthesis compete for the same DNA template, therefore being on a collision course. Unscheduled...

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Autores principales: Brambati, Alessandra, Colosio, Arianna, Zardoni, Luca, Galanti, Lorenzo, Liberi, Giordano
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4412130/
https://www.ncbi.nlm.nih.gov/pubmed/25972894
http://dx.doi.org/10.3389/fgene.2015.00166
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author Brambati, Alessandra
Colosio, Arianna
Zardoni, Luca
Galanti, Lorenzo
Liberi, Giordano
author_facet Brambati, Alessandra
Colosio, Arianna
Zardoni, Luca
Galanti, Lorenzo
Liberi, Giordano
author_sort Brambati, Alessandra
collection PubMed
description DNA replication and transcription are vital cellular processes during which the genetic information is copied into complementary DNA and RNA molecules. Highly complex machineries required for DNA and RNA synthesis compete for the same DNA template, therefore being on a collision course. Unscheduled replication–transcription clashes alter the gene transcription program and generate replication stress, reducing fork speed. Molecular pathways and mechanisms that minimize the conflict between replication and transcription have been extensively characterized in prokaryotic cells and recently identified also in eukaryotes. A pathological outcome of replication–transcription collisions is the formation of stable RNA:DNA hybrids in molecular structures called R-loops. Growing evidence suggests that R-loop accumulation promotes both genetic and epigenetic instability, thus severely affecting genome functionality. In the present review, we summarize the current knowledge related to replication and transcription conflicts in eukaryotes, their consequences on genome stability and the pathways involved in their resolution. These findings are relevant to clarify the molecular basis of cancer and neurodegenerative diseases.
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spelling pubmed-44121302015-05-13 Replication and transcription on a collision course: eukaryotic regulation mechanisms and implications for DNA stability Brambati, Alessandra Colosio, Arianna Zardoni, Luca Galanti, Lorenzo Liberi, Giordano Front Genet Genetics DNA replication and transcription are vital cellular processes during which the genetic information is copied into complementary DNA and RNA molecules. Highly complex machineries required for DNA and RNA synthesis compete for the same DNA template, therefore being on a collision course. Unscheduled replication–transcription clashes alter the gene transcription program and generate replication stress, reducing fork speed. Molecular pathways and mechanisms that minimize the conflict between replication and transcription have been extensively characterized in prokaryotic cells and recently identified also in eukaryotes. A pathological outcome of replication–transcription collisions is the formation of stable RNA:DNA hybrids in molecular structures called R-loops. Growing evidence suggests that R-loop accumulation promotes both genetic and epigenetic instability, thus severely affecting genome functionality. In the present review, we summarize the current knowledge related to replication and transcription conflicts in eukaryotes, their consequences on genome stability and the pathways involved in their resolution. These findings are relevant to clarify the molecular basis of cancer and neurodegenerative diseases. Frontiers Media S.A. 2015-04-28 /pmc/articles/PMC4412130/ /pubmed/25972894 http://dx.doi.org/10.3389/fgene.2015.00166 Text en Copyright © 2015 Brambati, Colosio, Zardoni, Galanti and Liberi. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Brambati, Alessandra
Colosio, Arianna
Zardoni, Luca
Galanti, Lorenzo
Liberi, Giordano
Replication and transcription on a collision course: eukaryotic regulation mechanisms and implications for DNA stability
title Replication and transcription on a collision course: eukaryotic regulation mechanisms and implications for DNA stability
title_full Replication and transcription on a collision course: eukaryotic regulation mechanisms and implications for DNA stability
title_fullStr Replication and transcription on a collision course: eukaryotic regulation mechanisms and implications for DNA stability
title_full_unstemmed Replication and transcription on a collision course: eukaryotic regulation mechanisms and implications for DNA stability
title_short Replication and transcription on a collision course: eukaryotic regulation mechanisms and implications for DNA stability
title_sort replication and transcription on a collision course: eukaryotic regulation mechanisms and implications for dna stability
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4412130/
https://www.ncbi.nlm.nih.gov/pubmed/25972894
http://dx.doi.org/10.3389/fgene.2015.00166
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