A structural solution for the DNA polymerase lambda-dependent repair of DNA gaps with minimal homology

Mol Cell. 2004 Feb 27;13(4):561-72. doi: 10.1016/s1097-2765(04)00061-9.

Abstract

Human DNA polymerase lambda (Pol lambda) is a family X member with low frameshift fidelity that has been suggested to perform gap-filling DNA synthesis during base excision repair and during repair of broken ends with limited homology. Here, we present a 2.1 A crystal structure of the catalytic core of Pol lambda in complex with DNA containing a two nucleotide gap. Pol lambda makes limited contacts with the template strand at the polymerase active site, and superimposition with Pol beta in a ternary complex suggests a shift in the position of the DNA at the active site that is reminiscent of a deletion intermediate. Surprisingly, Pol lambda can adopt a closed conformation, even in the absence of dNTP binding. These observations have implications for the catalytic mechanism and putative DNA repair functions of Pol lambda.

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Binding Sites
  • Conserved Sequence
  • Crystallography, X-Ray
  • DNA Polymerase beta / chemistry*
  • DNA Polymerase beta / metabolism
  • DNA Repair
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Molecular Weight
  • Nucleic Acid Conformation
  • Protein Binding
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Sequence Homology, Amino Acid
  • Static Electricity
  • Substrate Specificity

Substances

  • DNA polymerase beta2
  • DNA Polymerase beta

Associated data

  • PDB/1RZT