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Yale J Biol Med. 2013 Dec 13;86(4):443-51.

Hypoxia and DNA repair.

Author information

1
Department of Therapeutic Radiology, Yale School of Medicine, New Haven, Connecticut ; Department of Genetics, Yale School of Medicine, New Haven, Connecticut.
2
Department of Therapeutic Radiology, Yale School of Medicine, New Haven, Connecticut.

Abstract

Hypoxia is a characteristic feature of solid tumors and occurs very early in neoplastic development. Hypoxia transforms cell physiology in multiple ways, with profound changes in cell metabolism, cell growth, susceptibility to apoptosis, induction of angiogenesis, and increased motility. Over the past 20 years, our lab has determined that hypoxia also induces genetic instability. We have conducted a large series of experiments revealing that this instability occurs through the alteration of DNA repair pathways, including nucleotide excision repair, DNA mismatch repair, and homology dependent repair. Our work suggests that hypoxia, as a key component of solid tumors, can drive cancer progression through its impact on genomic integrity. However, the acquired changes in DNA repair that are induced by hypoxia may also render hypoxic cancer cells vulnerable to tailored strategies designed to exploit these changes.

KEYWORDS:

BRCA1; DNA repair; MLH1; epigenetics; homologous recombination; hypoxia; microRNAs; mismatch repair; silencing

PMID:
24348208
PMCID:
PMC3848098
[Indexed for MEDLINE]
Free PMC Article

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