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 lambda-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 Pol kappa is required for accurate translesion DNA synthesis past naturally occurring polycyclic guanine adducts, possibly generated by cholesterol and/or its metabolites.
journal_name
DNA Repair (Amst)journal_title
DNA repairauthors
Stancel JN,McDaniel LD,Velasco S,Richardson J,Guo C,Friedberg ECdoi
10.1016/j.dnarep.2009.09.003subject
Has Abstractpub_date
2009-12-03 00:00:00pages
1355-62issue
12eissn
1568-7864issn
1568-7856pii
S1568-7864(09)00238-9journal_volume
8pub_type
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