Impact of hypoxia on DNA repair and genome integrity

Abstract Hypoxia is a hallmark of the tumour microenvironment with profound effects on tumour biology, influencing cancer progression, the development of metastasis and patient outcome. Hypoxia also contributes to genomic instability and mutation frequency by inhibiting DNA repair pathways. This rev...

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Bibliographic Details
Published inMutagenesis Vol. 35; no. 1; pp. 61 - 68
Main Authors Kaplan, Alanna R, Glazer, Peter M
Format Journal Article
LanguageEnglish
Published UK Oxford University Press 13.02.2020
Subjects
Cell Hypoxia
DNA Mismatch Repair
DNA Repair
Gene Expression Regulation, Neoplastic
Genome
Genomic Instability
Humans
Molecular Targeted Therapy
Neoplasm Metastasis
Neoplasms - genetics
Neoplasms - metabolism
Neoplasms - pathology
Recombinational DNA Repair
Reviews
Tumor Hypoxia - drug effects
Tumor Microenvironment - genetics
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Summary:Abstract Hypoxia is a hallmark of the tumour microenvironment with profound effects on tumour biology, influencing cancer progression, the development of metastasis and patient outcome. Hypoxia also contributes to genomic instability and mutation frequency by inhibiting DNA repair pathways. This review summarises the diverse mechanisms by which hypoxia affects DNA repair, including suppression of homology-directed repair, mismatch repair and base excision repair. We also discuss the effects of hypoxia mimetics and agents that induce hypoxia on DNA repair, and we highlight areas of potential clinical relevance as well as future directions.
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ISSN:0267-8357
1464-3804
1464-3804
DOI:10.1093/mutage/gez019