Gene prophylaxis of endogenous DNA damage

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

A significant contribution to human mutagenesis and carcinogenesis may come from DNA damage of endogenous, rather than exogenous, origin. Efficient repair mechanisms have evolved to cope with it. The major pathway involved in DNA repair of endogenous damage is DNA base excision repair (BER). In addition, an important contribution is given by O6 alkylguanine DNA alkyltranferase, that repairs specifically the miscoding base O6 alkylguanine. BER is rather efficient in human cells but a certain amount of endogenous damage inevitably escapes mending and likely contributes to human carcinogenesis. Several attempts have been carried out to enhance the efficiency of repair of endogenous DNA damage by overexpressing in mammalian cells single enzymatic activities. In some cases (e.g. formamidopyrimidine DNA glycosylase or O6 alkylguanine DNA alkyltransferase) this approach turned out successful in improving cellular protection from endogenous and exogenous mutagens while overexpression of other enzymatic activities (e.g alkyl N-purine DNA glycosylase or DNA polymerase β) was detrimental and even produced a genome instability phenotype. Prophylaxis of endogenous DNA damage and mutation could be achieved in at-risk individuals by expression of appropriate DNA repair genes. Currently available vehicles for this peculiar type of gene therapy are surveyed.

Original languageEnglish
Title of host publicationNew Research on DNA Repair
PublisherNova Science Publishers, Inc.
Pages115-166
Number of pages52
ISBN (Print)9781600213854
Publication statusPublished - 2007

Keywords

  • 8-oxoguanine
  • Abasic sites
  • Adenovirus
  • Cancer
  • DNA base excision repair
  • DNA repair
  • Endogenous DNA damage
  • Gene therapy
  • Glycosylase
  • Lentivirus
  • Methylation
  • Mutation
  • O alkylguanine DNA alkyltransferase
  • Oxidation
  • Oxidative DNA damage
  • Rate-limiting step
  • Retrovirus
  • Transfection
  • Vector

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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