Completion of base excision repair by mammalian DNA ligases

Prog Nucleic Acid Res Mol Biol. 2001;68:151-64. doi: 10.1016/s0079-6603(01)68097-8.

Abstract

Three mammalian genes encoding DNA ligases--LIG1, LIG3, and LIG4--have been identified. Genetic, biochemical, and cell biology studies indicate that the products of each of these genes play a unique role in mammalian DNA metabolism. Interestingly, cell lines deficient in either DNA ligase I (46BR.1G1) or DNA ligase III (EM9) are sensitive to simple alkylating agents. One interpretation of these observations is that DNA ligases I and III participate in functionally distinct base excision repair (BER) subpathways. In support of this idea, extracts from both DNA ligase-deficient cell lines are defective in catalyzing BER in vitro and both DNA ligases interact with other BER proteins. DNA ligase I interacts directly with proliferating cell nuclear antigen (PCNA) and DNA polymerase beta (Pol beta), linking this enzyme with both short-patch and long-patch BER. In somatic cells, DNA ligase III alpha forms a stable complex with the DNA repair protein Xrcc1. Although Xrcc1 has no catalytic activity, it also interacts with Pol beta and poly(ADP-ribose) polymerase (PARP), linking DNA ligase III alpha with BER and single-strand break repair, respectively. Biochemical studies suggest that the majority of short-patch base excision repair events are completed by the DNA ligase III alpha/Xrcc1 complex. Although there is compelling evidence for the participation of PARP in the repair of DNA single-strand breaks, the role of PARP in BER has not been established.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • CHO Cells
  • Cell Line
  • Cloning, Molecular
  • Cricetinae
  • Cricetulus
  • DNA Damage
  • DNA Ligases / deficiency
  • DNA Ligases / genetics
  • DNA Ligases / physiology*
  • DNA Repair / genetics
  • DNA Repair / physiology*
  • DNA, Complementary / genetics
  • DNA-Binding Proteins / metabolism
  • Fibroblasts
  • Genes
  • Genetic Complementation Test
  • Humans
  • Isoenzymes / deficiency
  • Isoenzymes / genetics
  • Isoenzymes / physiology*
  • Macromolecular Substances
  • Mammals / genetics
  • Mammals / metabolism
  • Phenotype
  • X-ray Repair Cross Complementing Protein 1

Substances

  • DNA, Complementary
  • DNA-Binding Proteins
  • Isoenzymes
  • Macromolecular Substances
  • X-ray Repair Cross Complementing Protein 1
  • XRCC1 protein, human
  • DNA Ligases