Regulation and disregulation of mammalian nucleotide excision repair [electronic resource] : A pathway to nongermline breast carcinogenesis

Published:: Washington, D.C. : United States. Dept. of Energy, 2014.
Oak Ridge, Tenn. : Distributed by the Office of Scientific and Technical Information, U.S. Dept. of Energy
Physical Description:: pages 493-500 : digital, PDF file
Additional Creators:: Nova Research, Inc
United States. Department of Energy
United States. Department of Energy. Office of Scientific and Technical Information
Access Online:: www.osti.gov

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Summary:

Nucleotide excision repair (NER) is important as a modulator of disease, especially in constitutive deficiencies, such as the cancer predisposition syndrome Xeroderma pigmentosum. We have found profound variation of NER capacity among normal individuals, between cell-types and during carcinogenesis. NER is a repair system for many types of DNA damage, and therefore many types of genotoxic carcinogenic exposures, including ultraviolet light, products of organic combustion, metals, oxidative stress, etc. Since NER is intimately related to cellular metabolism, requiring components of both the DNA replicative and transcription machinery, it has a narrow range of functional viability. Thus, genes in the NER pathway are expressed at the low levels manifested by, for example, nuclear transcription factors. Since NER activity and gene expression vary by cell-type, it is inherently epigenetically regulated. Furthermore, this epigenetic regulation is disregulated during sporadic breast carcinogenesis. Loss of NER is one basis of genomic instability, a required element in cellular transformation, and one that potentially modulates response to therapy. In this article, we demonstrate differences in NER capacity in eight adult mouse tissues, and place this result into the context of our previous work on mouse extraembryonic tissues, normal human tissues and sporadic early stage human breast cancer.

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Published through SciTech Connect.
12/19/2014.
Photochemistry and Photobiology 91 2 ISSN 0031-8655 AM
Jean J. Latimer; Vongai J. Majekwana; Yashira R. Pabon-Padin; Manasi R. Pimpley; Stephen G. Grant.

Funding Information:

AC03-76SF01012

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