Dual roles for DNA polymerase eta in homologous DNA recombination and translesion DNA synthesis

Mol Cell. 2005 Dec 9;20(5):793-9. doi: 10.1016/j.molcel.2005.10.016.


Chicken B lymphocyte precursors and DT40 cells diversify their immunoglobulin-variable (IgV) genes through homologous recombination (HR)-mediated Ig gene conversion. To identify DNA polymerases that are involved in Ig gene conversion, we created DT40 clones deficient in DNA polymerase eta (poleta), which, in humans, is defective in the variant form of xeroderma pigmentosum (XP-V). Poleta is an error-prone translesion DNA synthesis polymerase that can bypass UV damage-induced lesions and is involved in IgV hypermutation. Like XP-V cells, poleta-disrupted (poleta) clones exhibited hypersensitivity to UV. Remarkably, poleta cells showed a significant decrease in the frequency of both Ig gene conversion and double-strand break-induced HR when compared to wild-type cells, and these defects were reversed by complementation with human poleta. Our findings identify a DNA polymerase that carries out DNA synthesis for physiological HR and provides evidence that a single DNA polymerase can play multiple cellular roles.

Publication types

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

MeSH terms

  • Animals
  • Base Sequence
  • Cell Line
  • Chickens
  • Cloning, Molecular
  • DNA / biosynthesis*
  • DNA / genetics
  • DNA / metabolism
  • DNA Damage / genetics
  • DNA Damage / radiation effects
  • DNA Repair / genetics
  • DNA Repair / physiology
  • DNA-Directed DNA Polymerase / genetics*
  • DNA-Directed DNA Polymerase / physiology*
  • DNA-Directed DNA Polymerase / radiation effects
  • Humans
  • Immunoglobulin Variable Region / genetics
  • Immunoglobulins / genetics
  • Immunoglobulins / radiation effects
  • Models, Genetic
  • Molecular Sequence Data
  • Mutation
  • Rad51 Recombinase / metabolism
  • Recombination, Genetic*
  • Ultraviolet Rays / adverse effects
  • Xeroderma Pigmentosum / genetics


  • Immunoglobulin Variable Region
  • Immunoglobulins
  • DNA
  • Rad51 Recombinase
  • DNA-Directed DNA Polymerase
  • Rad30 protein

Associated data

  • GENBANK/AB097589