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Transcription-Replication Collisions and Chromosome Fragility

Accurate replication of the entire genome is critical for cell division and propagation. Certain regions in the genome, such as fragile sites (common fragile sites, rare fragile sites, early replicating fragile sites), rDNA and telomeres, are intrinsically difficult to replicate, especially in the p...

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Autores principales: Wu, Wei, He, Jing Na, Lan, Mengjiao, Zhang, Pumin, Chu, Wai Kit
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8703014/
https://www.ncbi.nlm.nih.gov/pubmed/34956339
http://dx.doi.org/10.3389/fgene.2021.804547
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author Wu, Wei
He, Jing Na
Lan, Mengjiao
Zhang, Pumin
Chu, Wai Kit
author_facet Wu, Wei
He, Jing Na
Lan, Mengjiao
Zhang, Pumin
Chu, Wai Kit
author_sort Wu, Wei
collection PubMed
description Accurate replication of the entire genome is critical for cell division and propagation. Certain regions in the genome, such as fragile sites (common fragile sites, rare fragile sites, early replicating fragile sites), rDNA and telomeres, are intrinsically difficult to replicate, especially in the presence of replication stress caused by, for example, oncogene activation during tumor development. Therefore, these regions are particularly prone to deletions and chromosome rearrangements during tumorigenesis, rendering chromosome fragility. Although, the mechanism underlying their “difficult-to-replicate” nature and genomic instability is still not fully understood, accumulating evidence suggests transcription might be a major source of endogenous replication stress (RS) leading to chromosome fragility. Here, we provide an updated overview of how transcription affects chromosome fragility. Furthermore, we will use the well characterized common fragile sites (CFSs) as a model to discuss pathways involved in offsetting transcription-induced RS at these loci with a focus on the recently discovered atypical DNA synthesis repair pathway Mitotic DNA Synthesis (MiDAS).
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spelling pubmed-87030142021-12-25 Transcription-Replication Collisions and Chromosome Fragility Wu, Wei He, Jing Na Lan, Mengjiao Zhang, Pumin Chu, Wai Kit Front Genet Genetics Accurate replication of the entire genome is critical for cell division and propagation. Certain regions in the genome, such as fragile sites (common fragile sites, rare fragile sites, early replicating fragile sites), rDNA and telomeres, are intrinsically difficult to replicate, especially in the presence of replication stress caused by, for example, oncogene activation during tumor development. Therefore, these regions are particularly prone to deletions and chromosome rearrangements during tumorigenesis, rendering chromosome fragility. Although, the mechanism underlying their “difficult-to-replicate” nature and genomic instability is still not fully understood, accumulating evidence suggests transcription might be a major source of endogenous replication stress (RS) leading to chromosome fragility. Here, we provide an updated overview of how transcription affects chromosome fragility. Furthermore, we will use the well characterized common fragile sites (CFSs) as a model to discuss pathways involved in offsetting transcription-induced RS at these loci with a focus on the recently discovered atypical DNA synthesis repair pathway Mitotic DNA Synthesis (MiDAS). Frontiers Media S.A. 2021-12-10 /pmc/articles/PMC8703014/ /pubmed/34956339 http://dx.doi.org/10.3389/fgene.2021.804547 Text en Copyright © 2021 Wu, He, Lan, Zhang and Chu. https://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) and the copyright owner(s) 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
Wu, Wei
He, Jing Na
Lan, Mengjiao
Zhang, Pumin
Chu, Wai Kit
Transcription-Replication Collisions and Chromosome Fragility
title Transcription-Replication Collisions and Chromosome Fragility
title_full Transcription-Replication Collisions and Chromosome Fragility
title_fullStr Transcription-Replication Collisions and Chromosome Fragility
title_full_unstemmed Transcription-Replication Collisions and Chromosome Fragility
title_short Transcription-Replication Collisions and Chromosome Fragility
title_sort transcription-replication collisions and chromosome fragility
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8703014/
https://www.ncbi.nlm.nih.gov/pubmed/34956339
http://dx.doi.org/10.3389/fgene.2021.804547
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