PARP-1: Friend or Foe of DNA Damage and Repair in Tumorigenesis?
AbstractOxidative stress induced by reactive oxygen species can result in DNA damage within cells and subsequently increase risk for carcinogenesis. This may be averted by repair of DNA damage through the base or nucleotide excision repair (BER/NER) pathways. PARP, a BER protein, is known for its role in DNA-repair. However, multiple lesions can occur within a small range of DNA, known as oxidative clustered DNA lesions (OCDLs), which are difficult to repair and may lead to the more severe DNA double-strand break (DSB). Inefficient DSB repair can then result in increased mutagenesis and neoplastic transformation. OCDLs occur more frequently within a variety of tumor tissues. Interestingly, PARP is highly expressed in several human cancers. Additionally, chronic inflammation may contribute to tumorigenesis through ROS-induced DNA damage. Furthermore, PARP can modulate inflammation through interaction with NFκB and regulating the expression of inflammatory signaling molecules. Thus, the upregulation of PARP may present a double-edged sword. PARP is needed to repair ROS-induced DNA lesions, but PARP expression may lead to increased inflammation via upregulation of NFκB signaling. Here, we discuss the role of PARP in the repair of oxidative damage versus the formation of OCDLs and speculate on the feasibility of PARP inhibition for the treatment and prevention of cancers by exploiting its role in inflammation.
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Swindall, A.F.; Stanley, J.A.; Yang, E.S. PARP-1: Friend or Foe of DNA Damage and Repair in Tumorigenesis? Cancers 2013, 5, 943-958.
Swindall AF, Stanley JA, Yang ES. PARP-1: Friend or Foe of DNA Damage and Repair in Tumorigenesis? Cancers. 2013; 5(3):943-958.Chicago/Turabian Style
Swindall, Amanda F.; Stanley, Jennifer A.; Yang, Eddy S. 2013. "PARP-1: Friend or Foe of DNA Damage and Repair in Tumorigenesis?" Cancers 5, no. 3: 943-958.