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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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2015
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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. |
format | Online Article Text |
id | pubmed-4412130 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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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