Mouse DNA polymerase kappa has a functional role in the repair of DNA strand breaks

DNA Repair (Amst). 2013 May 1;12(5):377-88. doi: 10.1016/j.dnarep.2013.02.008. Epub 2013 Mar 21.


The Y-family of DNA polymerases support of translesion DNA synthesis (TLS) associated with stalled DNA replication by DNA damage. Recently, a number of studies suggest that some specialized TLS polymerases also support other aspects of DNA metabolism beyond TLS in vivo. Here we show that mouse polymerase kappa (Polκ) could accumulate at laser-induced sites of damage in vivo resembling polymerases eta and iota. The recruitment was mediated through Polκ C-terminus which contains the PCNA-interacting peptide, ubiquitin zinc finger motif 2 and nuclear localization signal. Interestingly, this recruitment was significantly reduced in MSH2-deficient LoVo cells and Rad18-depleted cells. We further observed that Polκ-deficient mouse embryo fibroblasts were abnormally sensitive to H2O2 treatment and displayed defects in both single-strand break repair and double-strand break repair. We speculate that Polκ may have an important role in strand break repair following oxidative stress in vivo.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • DNA Breaks, Double-Stranded*
  • DNA Breaks, Single-Stranded*
  • DNA Repair*
  • DNA-Binding Proteins / metabolism
  • DNA-Directed DNA Polymerase / chemistry
  • DNA-Directed DNA Polymerase / genetics
  • DNA-Directed DNA Polymerase / metabolism*
  • Embryonic Stem Cells / drug effects
  • Embryonic Stem Cells / metabolism
  • Hydrogen Peroxide / pharmacology
  • Lasers
  • Mice
  • Mice, Knockout
  • MutS Homolog 2 Protein / metabolism
  • Nuclear Localization Signals
  • Oxidative Stress
  • Proliferating Cell Nuclear Antigen / metabolism
  • Protein Structure, Tertiary


  • DNA-Binding Proteins
  • Nuclear Localization Signals
  • Proliferating Cell Nuclear Antigen
  • Rad18 protein, mouse
  • Hydrogen Peroxide
  • DNA-Directed DNA Polymerase
  • Polk protein, mouse
  • Msh2 protein, mouse
  • MutS Homolog 2 Protein