Authors: Kristin L. Lockett; Isaac V. Snowhite; Jennifer J. Hu

Source: Current Pharmacogenomics, Volume 3, Number 1, March 2005 , pp. 9-19(11)

Publisher: Bentham Science Publishers

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

Document Type: Review article

DOI: http://dx.doi.org/10.2174/1570160053175054

Affiliations: 1: Louisiana State University Health Sciences Center, School of Public Health and Stanley S. Scott Cancer Center, 533 Bolivar Street, CSRB-454, New Orleans, Louisiana 70112, USA.

Publication date: 2005-03-01

More about this publication?

• Current Pharmacogenomics provides comprehensive overviews of all current research on pharmacogenomics and pharmacogenetics. All areas of the field from pre-clinical to clinical research are covered, including related areas such as genomics, proteomics, target discovery, bioinformatics and novel diagnostics. This international journal is peer-reviewed and publishes both mini- and full review articles.
  
  The journal has become essential reading for all researchers and clinicians with interests in pharmacogenomics and pharmacogenetics.

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