Comparison of functional properties of mammalian DNA polymerase lambda and DNA polymerase beta in reactions of DNA synthesis related to DNA repair

Biochim Biophys Acta. 2005 Aug 10;1751(2):150-8. doi: 10.1016/j.bbapap.2005.05.012.


DNA polymerase lambda (Pol lambda) is a novel enzyme of the family X of DNA polymerases. Pol lambda has some properties in common with DNA polymerase beta (Pol beta). The substrate properties of Pol lambda were compared to Pol beta using DNAs mimicking short-patch (SP) and long-patch (LP) base excision repair (BER) intermediates as well as recessed template primers. In the present work, the influence of several BER proteins such as flap-endonuclease-1 (FEN1), PCNA, and apurinic/apyrimidinic endonuclease-1 (APE1) on the activity of Pol lambda was investigated. Pol lambda is unable to catalyze strand displacement synthesis using nicked DNA, although this enzyme efficiently incorporates a dNMP into a one-nucleotide gap. FEN1 and PCNA stimulate the strand displacement activity of Pol lambda. FEN1 processes nicked DNA, thus removing a barrier to Pol lambda DNA synthesis. It results in a one-nucleotide gapped DNA molecule that is a favorite substrate of Pol lambda. Photocrosslinking and functional assay show that Pol lambda is less efficient than Pol beta in binding to nicked DNA. APE1 has no influence on the strand displacement activity of Pol lambda though it stimulates strand displacement synthesis catalyzed with Pol beta. It is suggested that Pol lambda plays a role in the SP BER rather than contributes to the LP BER pathway.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cations, Divalent / chemistry
  • DNA / biosynthesis*
  • DNA / chemistry
  • DNA Polymerase beta / chemistry
  • DNA Polymerase beta / genetics
  • DNA Polymerase beta / metabolism*
  • DNA Primers / chemistry
  • DNA Primers / genetics
  • DNA Primers / metabolism
  • DNA Repair*
  • DNA-(Apurinic or Apyrimidinic Site) Lyase / chemistry
  • DNA-(Apurinic or Apyrimidinic Site) Lyase / genetics
  • DNA-(Apurinic or Apyrimidinic Site) Lyase / metabolism
  • Deoxycytosine Nucleotides / chemistry
  • Flap Endonucleases / chemistry
  • Flap Endonucleases / genetics
  • Flap Endonucleases / metabolism
  • Humans
  • Molecular Sequence Data
  • Photoaffinity Labels / chemistry
  • Proliferating Cell Nuclear Antigen / chemistry
  • Proliferating Cell Nuclear Antigen / genetics
  • Proliferating Cell Nuclear Antigen / metabolism
  • Rats
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Substrate Specificity


  • Cations, Divalent
  • DNA Primers
  • Deoxycytosine Nucleotides
  • Photoaffinity Labels
  • Proliferating Cell Nuclear Antigen
  • Recombinant Proteins
  • 2'-deoxycytidine 5'-triphosphate
  • DNA
  • DNA polymerase beta2
  • DNA Polymerase beta
  • Flap Endonucleases
  • DNA-(Apurinic or Apyrimidinic Site) Lyase