The DNA ligase III zinc finger stimulates binding to DNA secondary structure and promotes end joining

Nucleic Acids Res. 2000 Sep 15;28(18):3558-63. doi: 10.1093/nar/28.18.3558.

Abstract

The ability to rejoin broken chromosomes is fundamental to the maintenance of genetic integrity. Mammalian cells possess at least five DNA ligases, including three isoforms of DNA ligase III (Lig-3). Lig-3 proteins differ from other DNA ligases in the presence of an N-terminal zinc finger (Zn-f) motif that exhibits extensive homology with two zinc fingers in poly(ADP-ribose) polymerase (PARP). Here we report that the Zn-f confers upon Lig-3 the ability to bind DNA duplexes harbouring a variety of DNA secondary structures, including single-strand gaps and single-strand flaps. Moreover, the Zn-f stimulates intermolecular end joining of duplexes that harbour these structures up to 16-fold. The Zn-f also stimulates end joining between duplexes lacking secondary structure, but to a lesser extent (up to 4-fold). We conclude that the Zn-f may enable Lig-3 to rejoin chromosomal DNA strand breaks located at sites of clustered damage induced by ionising radiation or near to secondary structure intermediates of DNA metabolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA / chemistry
  • DNA / metabolism*
  • DNA Ligase ATP
  • DNA Ligases / genetics
  • DNA Ligases / metabolism*
  • DNA Repair
  • Humans
  • Nucleic Acid Conformation
  • Poly-ADP-Ribose Binding Proteins
  • Protein Binding
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Xenopus Proteins
  • Zinc Fingers*

Substances

  • Poly-ADP-Ribose Binding Proteins
  • Recombinant Proteins
  • Xenopus Proteins
  • DNA
  • DNA Ligases
  • DNA Ligase ATP
  • DNA ligase III alpha protein, Xenopus
  • LIG3 protein, human