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 language | English (US) |
|---|---|
| Pages (from-to) | 1355-1362 |
| Number of pages | 8 |
| Journal | DNA Repair |
| Volume | 8 |
| Issue number | 12 |
| DOIs | |
| State | Published - Dec 3 2009 |
Fingerprint
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 journal › Article
}
TY - JOUR
T1 - Polk mutant mice have a spontaneous mutator phenotype
AU - Stancel, J. Nicole Kosarek
AU - McDaniel, Lisa D.
AU - Velasco, Susana
AU - Richardson, James
AU - Guo, Caixia
AU - Friedberg, Errol C.
PY - 2009/12/3
Y1 - 2009/12/3
N2 - 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.
AB - 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.
KW - DNA polymerase kappa
KW - Mutagenesis
KW - Polk mutant mice
KW - Translesion DNA synthesis
UR - http://www.scopus.com/inward/record.url?scp=70450222118&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=70450222118&partnerID=8YFLogxK
U2 - 10.1016/j.dnarep.2009.09.003
DO - 10.1016/j.dnarep.2009.09.003
M3 - Article
C2 - 19783230
AN - SCOPUS:70450222118
VL - 8
SP - 1355
EP - 1362
JO - DNA Repair
JF - DNA Repair
SN - 1568-7864
IS - 12
ER -