The Genetic Regulation of ADPRT/PARP-1 in Aging and Cancer Susceptibility

Author(s): Kristin L. Lockett, Isaac V. Snowhite, Jennifer J. Hu.

Journal Name: Current Pharmacogenomics

Volume 3 , Issue 1 , 2005

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Abstract:

The ADP-ribosyltransferase (ADPRT) gene encodes the poly(ADP-ribose)polymerase-1 (PARP-1) enzyme, which plays critical roles in DNA-damage signaling and repair, cell death, maintenance of genomic stability, and carcinogenesis. It may also serve as a potential target for cancer therapy. In this review, we evaluate findings from animal model systems and molecular epidemiological studies to demonstrate the potential role of ADPRT/PARP-1 in aging and carcinogenesis. With increasing interest in associating human cancer risk with single nucleotide polymorphisms (SNPs) and/or dysfunction of ADPRT/PARP-1, several important technical challenges will need to be overcome. These challenges include developing specific functional assays, selecting SNPs with potential functional impact, and exploring statistical methods for gene-gene and gene-environmental interactions. Therefore, this review also highlights strategies to evaluate the functional significance of ADPRT/PARP-1 SNPs in human cancer risk assessment. In summary, dysfunction of PARP-1 may play a critical role in abnormal cellular functions; its molecular mechanism in aging and cancer susceptibility is an issue which needs urgently to be elucidated.

Keywords: signaling, tumor suppressor genes, nicotinamide adenine dinucleotide, dna repair, necrosis, chromosomal aberrations, cancer, expression, polymorphism, adp-ribosylation

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Article Details

VOLUME: 3
ISSUE: 1
Year: 2005
Page: [9 - 19]
Pages: 11
DOI: 10.2174/1570160053175054

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