Impact of G-Quadruplexes and Chronic Inflammation on Genome Instability: Additive Effects during Carcinogenesis

Genome instability is an enabling characteristic of cancer, essential for cancer cell evolution. Hotspots of genome instability, from small-scale point mutations to large-scale structural variants, are associated with sequences that potentially form non-B DNA structures. G-quadruplex (G4) forming mo...

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Autores principales:	MaryElizabeth Stein, Kristin A. Eckert
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	G-quadruplex oxidative stress genome instability DNA polymerases Genetics QH426-470
Acceso en línea:	https://doaj.org/article/5d8f76ef098847adbbdd6627198923d1
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spelling	oai:doaj.org-article:5d8f76ef098847adbbdd6627198923d12021-11-25T17:41:53ZImpact of G-Quadruplexes and Chronic Inflammation on Genome Instability: Additive Effects during Carcinogenesis10.3390/genes121117792073-4425https://doaj.org/article/5d8f76ef098847adbbdd6627198923d12021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4425/12/11/1779https://doaj.org/toc/2073-4425Genome instability is an enabling characteristic of cancer, essential for cancer cell evolution. Hotspots of genome instability, from small-scale point mutations to large-scale structural variants, are associated with sequences that potentially form non-B DNA structures. G-quadruplex (G4) forming motifs are enriched at structural variant endpoints in cancer genomes. Chronic inflammation is a physiological state underlying cancer development, and oxidative DNA damage is commonly invoked to explain how inflammation promotes genome instability. We summarize where G4s and oxidative stress overlap, with a focus on DNA replication. Guanine has low ionization potential, making G4s vulnerable to oxidative damage. Impacts to G4 structure are dependent upon lesion type, location, and G4 conformation. Occasionally, G4s pose a challenge to replicative DNA polymerases, requiring specialized DNA polymerases to maintain genome stability. Therefore, chronic inflammation creates a dual challenge for DNA polymerases to maintain genome stability: faithful G4 synthesis and bypassing unrepaired oxidative lesions. Inflammation is also accompanied by global transcriptome changes that may impact mutagenesis. Several studies suggest a regulatory role for G4s within cancer- and inflammatory-related gene promoters. We discuss the extent to which inflammation could influence gene regulation by G4s, thereby impacting genome instability, and highlight key areas for new investigation.MaryElizabeth SteinKristin A. EckertMDPI AGarticleG-quadruplexoxidative stressgenome instabilityDNA polymerasesGeneticsQH426-470ENGenes, Vol 12, Iss 1779, p 1779 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	G-quadruplex oxidative stress genome instability DNA polymerases Genetics QH426-470
spellingShingle	G-quadruplex oxidative stress genome instability DNA polymerases Genetics QH426-470 MaryElizabeth Stein Kristin A. Eckert Impact of G-Quadruplexes and Chronic Inflammation on Genome Instability: Additive Effects during Carcinogenesis
description	Genome instability is an enabling characteristic of cancer, essential for cancer cell evolution. Hotspots of genome instability, from small-scale point mutations to large-scale structural variants, are associated with sequences that potentially form non-B DNA structures. G-quadruplex (G4) forming motifs are enriched at structural variant endpoints in cancer genomes. Chronic inflammation is a physiological state underlying cancer development, and oxidative DNA damage is commonly invoked to explain how inflammation promotes genome instability. We summarize where G4s and oxidative stress overlap, with a focus on DNA replication. Guanine has low ionization potential, making G4s vulnerable to oxidative damage. Impacts to G4 structure are dependent upon lesion type, location, and G4 conformation. Occasionally, G4s pose a challenge to replicative DNA polymerases, requiring specialized DNA polymerases to maintain genome stability. Therefore, chronic inflammation creates a dual challenge for DNA polymerases to maintain genome stability: faithful G4 synthesis and bypassing unrepaired oxidative lesions. Inflammation is also accompanied by global transcriptome changes that may impact mutagenesis. Several studies suggest a regulatory role for G4s within cancer- and inflammatory-related gene promoters. We discuss the extent to which inflammation could influence gene regulation by G4s, thereby impacting genome instability, and highlight key areas for new investigation.
format	article
author	MaryElizabeth Stein Kristin A. Eckert
author_facet	MaryElizabeth Stein Kristin A. Eckert
author_sort	MaryElizabeth Stein
title	Impact of G-Quadruplexes and Chronic Inflammation on Genome Instability: Additive Effects during Carcinogenesis
title_short	Impact of G-Quadruplexes and Chronic Inflammation on Genome Instability: Additive Effects during Carcinogenesis
title_full	Impact of G-Quadruplexes and Chronic Inflammation on Genome Instability: Additive Effects during Carcinogenesis
title_fullStr	Impact of G-Quadruplexes and Chronic Inflammation on Genome Instability: Additive Effects during Carcinogenesis
title_full_unstemmed	Impact of G-Quadruplexes and Chronic Inflammation on Genome Instability: Additive Effects during Carcinogenesis
title_sort	impact of g-quadruplexes and chronic inflammation on genome instability: additive effects during carcinogenesis
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/5d8f76ef098847adbbdd6627198923d1
work_keys_str_mv	AT maryelizabethstein impactofgquadruplexesandchronicinflammationongenomeinstabilityadditiveeffectsduringcarcinogenesis AT kristinaeckert impactofgquadruplexesandchronicinflammationongenomeinstabilityadditiveeffectsduringcarcinogenesis
_version_	1718412106008625152

Impact of G-Quadruplexes and Chronic Inflammation on Genome Instability: Additive Effects during Carcinogenesis

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