The DNA polymerase lambda is required for the repair of non-compatible DNA double strand breaks by NHEJ in mammalian cells

Nucleic Acids Res. 2006 May 31;34(10):2998-3007. doi: 10.1093/nar/gkl380. Print 2006.


DNA polymerase lambda (pollambda) is a recently identified DNA polymerase whose cellular function remains elusive. Here we show, that pollambda participates at the molecular level in a chromosomal context, in the repair of DNA double strand breaks (DSB) via non-homologous end joining (NHEJ) in mammalian cells. The expression of a catalytically inactive form of pollambda (pollambdaDN) decreases the frequency of NHEJ events in response to I-Sce-I-induced DSB whereas inactivated forms of its homologues polbeta and polmu do not. Only events requiring DNA end processing before ligation are affected; this defect is associated with large deletions arising in the vicinity of the induced DSB. Furthermore, pollambdaDN-expressing cells exhibit increased sensitization and genomic instability in response to ionizing radiation similar to that of NHEJ-defective cells. Our data support a requirement for pollambda in repairing a subset of DSB in genomic DNA, thereby contributing to the maintenance of genetic stability mediated by the NHEJ pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Camptothecin / toxicity
  • DNA / chemistry
  • DNA Damage
  • DNA Polymerase beta / genetics
  • DNA Polymerase beta / metabolism
  • DNA Polymerase beta / physiology*
  • DNA Repair*
  • DNA-Directed DNA Polymerase / genetics
  • DNA-Directed DNA Polymerase / metabolism
  • Deoxyribonucleases, Type II Site-Specific / metabolism
  • Genomic Instability
  • Molecular Sequence Data
  • Mutation
  • Radiation, Ionizing
  • Recombination, Genetic*
  • Saccharomyces cerevisiae Proteins


  • Saccharomyces cerevisiae Proteins
  • DNA
  • DNA polymerase beta2
  • DNA polymerase mu
  • DNA Polymerase beta
  • DNA-Directed DNA Polymerase
  • SCEI protein, S cerevisiae
  • Deoxyribonucleases, Type II Site-Specific
  • Camptothecin