Impact of hypoxia on DNA repair and genome integrity

Author:

Kaplan Alanna R12,Glazer Peter M13

Affiliation:

1. Department of Therapeutic Radiology, New Haven, CT, USA

2. Department of Experimental Pathology, New Haven, CT, USA

3. Department of Genetics, Yale University, New Haven, CT, USA

Abstract

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.

Funder

National Institutes of Health

NIH Medical Scientist Training Program Training

Publisher

Oxford University Press (OUP)

Subject

Health, Toxicology and Mutagenesis,Genetics(clinical),Toxicology,Genetics

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