DNA polymerase lambda can elongate on DNA substrates mimicking non-homologous end joining and interact with XRCC4-ligase IV complex

Biochem Biophys Res Commun. 2004 Oct 29;323(4):1328-33. doi: 10.1016/j.bbrc.2004.09.002.

Abstract

Non-homologous end joining (NHEJ) is one of two pathways responsible for the repair of double-strand breaks in eukaryotic cells. The mechanism involves the alignment of broken DNA ends with minimal homology, fill in of short gaps by DNA polymerase(s), and ligation by XRCC4-DNA ligase IV complex. The gap-filling polymerase has not yet been positively identified, but recent biochemical studies have implicated DNA polymerase lambda (pol lambda), a novel DNA polymerase that has been assigned to the pol X family, in this process. Here we demonstrate that purified pol lambda can efficiently catalyze gap-filling synthesis on DNA substrates mimicking NHEJ. By designing two truncated forms of pol lambda, we also show that the unique proline-rich region in pol lambda plays a role in limiting strand displacement synthesis, a feature that may help its participation in in vivo NHEJ. Moreover, pol lambda interacts with XRCC4-DNA ligase IV via its N-terminal BRCT domain and the interaction stimulates the DNA synthesis activity of pol lambda. Taken together, these data strongly support that pol lambda functions in DNA polymerization events during NHEJ.

MeSH terms

  • Binding Sites
  • Biomimetic Materials / chemistry*
  • Catalysis
  • DNA / chemical synthesis
  • DNA / chemistry*
  • DNA Ligase ATP
  • DNA Ligases / chemistry*
  • DNA Polymerase gamma
  • DNA Repair*
  • DNA-Binding Proteins / chemistry*
  • DNA-Directed DNA Polymerase / chemistry*
  • Protein Binding
  • Substrate Specificity

Substances

  • DNA-Binding Proteins
  • LIG4 protein, human
  • XRCC4 protein, human
  • DNA
  • DNA Polymerase gamma
  • DNA-Directed DNA Polymerase
  • DNA Ligases
  • DNA Ligase ATP