Interrogation of nucleotide excision repair capacity: Impact on platinum-based cancer therapy

Jennifer N. Earley, John Turchi

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

DNA repair is essential for routine monitoring and repair of damage imparted to our genetic material by exposure to endogenous and exogenous carcinogens, including reactive oxygen species, UV light, and chemicals such as those found in cigarette smoke. Without DNA repair pathways, the continual assault on our DNA would be highly mutagenic and the risk of cancer increased. Paradoxically, the same pathways that help prevent cancer development are detrimental to the efficacy of DNA-damaging cancer therapeutics such as cisplatin. Recent studies demonstrate the inverse relationship between DNA repair capacity and efficacy of platinum-based chemotherapeutics: increased DNA repair capacity leads to resistance, while decreased capacity leads to increased sensitivities. Cisplatin's cytotoxic effects are mediated by formation of intrastrand DNA crosslinks, which are predominantly repaired via the nucleotide excision repair (NER) pathway. In an effort to personalize the treatment of cancers based on DNA repair capacity, we developed an ELISA-based assay to measure NER activity accurately and reproducibly as a prognostic for platinum-based treatments. Here we present an overview of DNA repair and its link to cancer and therapeutics. We also present data demonstrating the ability to detect the proteins of the pre-incision complex within the NER pathway from cell and tissue extracts.

Original languageEnglish
Pages (from-to)2465-2477
Number of pages13
JournalAntioxidants and Redox Signaling
Volume14
Issue number12
DOIs
StatePublished - Jun 15 2011

Fingerprint

Platinum
DNA Repair
Repair
Nucleotides
DNA
Neoplasms
Therapeutics
Cisplatin
Tissue Extracts
Ultraviolet Rays
Cell Extracts
Smoke
Tobacco Products
Carcinogens
Ultraviolet radiation
Reactive Oxygen Species
Assays
Enzyme-Linked Immunosorbent Assay
Monitoring
Genes

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Physiology
  • Clinical Biochemistry

Cite this

Interrogation of nucleotide excision repair capacity : Impact on platinum-based cancer therapy. / Earley, Jennifer N.; Turchi, John.

In: Antioxidants and Redox Signaling, Vol. 14, No. 12, 15.06.2011, p. 2465-2477.

Research output: Contribution to journalArticle

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