Polk mutant mice have a spontaneous mutator phenotype

J. Nicole Kosarek Stancel, Lisa D. McDaniel, Susana Velasco, James Richardson, Caixia Guo, Errol C. Friedberg

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Mice defective for the Polk gene, which encodes DNA polymerase kappa, are viable and do not manifest obvious phenotypes. The present studies document a spontaneous mutator phenotype in Polk-/- mice. The initial indication of enhanced spontaneous mutations in these mice came from the serendipitous observation of a postulated founder mutation that manifested in multiple disease states among a cohort of mice comprising all three possible Polk genotypes. Polk-/- and isogenic wild-type controls carrying a reporter transgene (the λ-phage cII gene) were used for subsequent quantitative and qualitative studies on mutagenesis in various tissues. We observed significantly increased mutation frequencies in the kidney, liver, and lung of Polk-/- mice, but not in the spleen or testis. G:C base pairs dominated the mutation spectra of the kidney, liver, and lung. These results are consistent with the notion that Polκ is required for accurate translesion DNA synthesis past naturally occurring polycyclic guanine adducts, possibly generated by cholesterol and/or its metabolites.

Original languageEnglish (US)
Pages (from-to)1355-1362
Number of pages8
JournalDNA Repair
Volume8
Issue number12
DOIs
StatePublished - Dec 3 2009

Fingerprint

Liver
Genes
Phenotype
Mutagenesis
Bacteriophages
Guanine
DNA-Directed DNA Polymerase
Metabolites
Cholesterol
Mutation
Tissue
DNA
Kidney
Lung
Mutation Rate
Transgenes
Base Pairing
Testis
Spleen
Genotype

Keywords

  • DNA polymerase kappa
  • Mutagenesis
  • Polk mutant mice
  • Translesion DNA synthesis

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Polk mutant mice have a spontaneous mutator phenotype. / Stancel, J. Nicole Kosarek; McDaniel, Lisa D.; Velasco, Susana; Richardson, James; Guo, Caixia; Friedberg, Errol C.

In: DNA Repair, Vol. 8, No. 12, 03.12.2009, p. 1355-1362.

Research output: Contribution to journalArticle

Stancel, J. Nicole Kosarek ; McDaniel, Lisa D. ; Velasco, Susana ; Richardson, James ; Guo, Caixia ; Friedberg, Errol C. / Polk mutant mice have a spontaneous mutator phenotype. In: DNA Repair. 2009 ; Vol. 8, No. 12. pp. 1355-1362.
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