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Cancers 2013, 5(3), 943-958; doi:10.3390/cancers5030943
Review

PARP-1: Friend or Foe of DNA Damage and Repair in Tumorigenesis?

1
, 1
 and 1,2,3,*
Received: 3 May 2013; in revised form: 17 July 2013 / Accepted: 19 July 2013 / Published: 26 July 2013
(This article belongs to the Special Issue Role of Oxidatively-Induced DNA Damage in Carcinogenesis)
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Abstract: Oxidative 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.
Keywords: PARP-1; oxidative clustered DNA lesions; inflammation; NFκB; PARP inhibitor; reactive oxygen species; ROS PARP-1; oxidative clustered DNA lesions; inflammation; NFκB; PARP inhibitor; reactive oxygen species; ROS
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

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.

AMA Style

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.



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