title: Hypoxia and DNA repair.
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.
authors.affiliation: Department of Therapeutic Radiology, Yale School of Medicine, New Haven, Connecticut ; Department of Genetics, Yale School of Medicine, New Haven, Connecticut.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Glazer
authors.affiliation: Department of Therapeutic Radiology, Yale School of Medicine, New Haven, Connecticut.
authors.forename: Denise C
authors.initials: DC
authors.lastname: Hegan
authors.affiliation: Department of Therapeutic Radiology, Yale School of Medicine, New Haven, Connecticut.
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Therapeutic Radiology, Yale School of Medicine, New Haven, Connecticut ; Department of Genetics, Yale School of Medicine, New Haven, Connecticut.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Czochor
authors.affiliation: Department of Therapeutic Radiology, Yale School of Medicine, New Haven, Connecticut ; Department of Genetics, Yale School of Medicine, New Haven, Connecticut.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Scanlon
mesh_terms: D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D004260:DNA Repair / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D042822:Genomic Instability; D006801:Humans; D000860:Hypoxia; D008957:Models, Genetic; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000235:genetics
keywords: BRCA1; DNA repair; MLH1; epigenetics; homologous recombination; hypoxia; microRNAs; mismatch repair; silencing