Mammalian dna repair enzymes

Anthony E. Pegg, Richard A. Bennett

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

The repair of damaged DNA is a vast field which has been extensively covered by reviews (a few recent examples are references 1-9) but is expanding very rapidly. This article is confined to DNA repair reactions occurring in mammalian cells which have been investigated with the aid of cell-free preparations and for which evidence of the nature of the enzymatic reaction taking place has been obtained. This criterion leads to the exclusion of many fascinating and extremely important experiments in which the repair of DNA damaged by ultraviolet (UV) or X-ray radiation and chemicals has been studied in detail at the cellular level. Many of these studies have substantial clinical relevance bearing on the biochemical basis of certain heritable diseases but these are fully covered in recent reviews. The restriction of this article to mammalian enzymes also excludes many pioneering studies of DNA repair in microorganisms some of which have provided the basis of the subsequent work in higher organisms. Some comparisons have been made in the present paper with equivalent enzymes in bacteria, and DNA repair in prokaryotes is covered in another chapter of this book. The present chapter covers enzymes involved in the initial removal of abnormal DNA bases and in the production of gaps in one strand of the DNA. Such gaps are filled in, requiring resynthesis by a DNA polymerase and ligation. It appears likely that DNA polymerase β carries out this resynthesis 10 and this is discussed elsewhere in this volume. The repair of DNA in eukaryotes may be complicated by the presence of a substantial part of the DNA within the complex chromatin structure. Evidence that DNA within nucleosomes can be repaired and that the kinetics of such repair may be different from that of extranucleosomal DNA has been published 11-15 but, at present, hard data implicating specific factors for making chromatin DNA available for repair is lacking. We have indicated where possible the results of comparisons with chromatin and naked DNA substrates with the enzymes described in this chapter. For each of the enzymes discussed we describe the reactions catalyzed, cofactors required, characteristics of the protein, and its purification and the regulation of activity under physiological or pathophysiological conditions.

Original languageEnglish (US)
Title of host publicationEnzymes of Nucleic Acid Synthesis and Modification
Subtitle of host publicationVolume 1: DNA Enzymes
PublisherCRC Press
Pages179-205
Number of pages27
ISBN (Electronic)9781315892306
ISBN (Print)0849355176, 9781315892757
DOIs
StatePublished - Jan 1 2018

All Science Journal Classification (ASJC) codes

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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    Pegg, A. E., & Bennett, R. A. (2018). Mammalian dna repair enzymes. In Enzymes of Nucleic Acid Synthesis and Modification: Volume 1: DNA Enzymes (pp. 179-205). CRC Press. https://doi.org/10.1201/9781351071857