Cargando…

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

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 DN...

Descripción completa

Detalles Bibliográficos
Autores principales: Swindall, Amanda F., Stanley, Jennifer A., Yang, Eddy S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3795373/
https://www.ncbi.nlm.nih.gov/pubmed/24202328
http://dx.doi.org/10.3390/cancers5030943
_version_ 1782287370709630976
author Swindall, Amanda F.
Stanley, Jennifer A.
Yang, Eddy S.
author_facet Swindall, Amanda F.
Stanley, Jennifer A.
Yang, Eddy S.
author_sort Swindall, Amanda F.
collection PubMed
description 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.
format Online
Article
Text
id pubmed-3795373
institution National Center for Biotechnology Information
language English
publishDate 2013
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-37953732013-10-21 PARP-1: Friend or Foe of DNA Damage and Repair in Tumorigenesis? Swindall, Amanda F. Stanley, Jennifer A. Yang, Eddy S. Cancers (Basel) Review 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. MDPI 2013-07-26 /pmc/articles/PMC3795373/ /pubmed/24202328 http://dx.doi.org/10.3390/cancers5030943 Text en © 2013 by the authors; licensee MDPI, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0/ This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Review
Swindall, Amanda F.
Stanley, Jennifer A.
Yang, Eddy S.
PARP-1: Friend or Foe of DNA Damage and Repair in Tumorigenesis?
title PARP-1: Friend or Foe of DNA Damage and Repair in Tumorigenesis?
title_full PARP-1: Friend or Foe of DNA Damage and Repair in Tumorigenesis?
title_fullStr PARP-1: Friend or Foe of DNA Damage and Repair in Tumorigenesis?
title_full_unstemmed PARP-1: Friend or Foe of DNA Damage and Repair in Tumorigenesis?
title_short PARP-1: Friend or Foe of DNA Damage and Repair in Tumorigenesis?
title_sort parp-1: friend or foe of dna damage and repair in tumorigenesis?
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3795373/
https://www.ncbi.nlm.nih.gov/pubmed/24202328
http://dx.doi.org/10.3390/cancers5030943
work_keys_str_mv AT swindallamandaf parp1friendorfoeofdnadamageandrepairintumorigenesis
AT stanleyjennifera parp1friendorfoeofdnadamageandrepairintumorigenesis
AT yangeddys parp1friendorfoeofdnadamageandrepairintumorigenesis