The genetic regulation of ADPRT/PARP-1 in aging and cancer susceptibility

Kristin L. Lockett, Isaac V. Snowhite, Jennifer J. Hu

Research output: Contribution to journalReview article

1 Scopus citations

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 SNP's 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 SNP's 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.

Original languageEnglish (US)
Pages (from-to)9-19
Number of pages11
JournalCurrent Pharmacogenomics
Volume3
Issue number1
DOIs
StatePublished - Mar 1 2005
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Pharmacology

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