Murine Prkdc polymorphisms impact DNA-PKcs function

Kristin M. Fabre, Lila Ramaiah, Ryan C. Dregalla, Christian Desaintes, Michael M. Weil, Susan M. Bailey, Robert L. Ullrich

Research output: Contribution to journalArticle

9 Scopus citations


Polymorphic variants of DNA repair genes can increase the carcinogenic potential of exposure to ionizing radiation. Two single nucleotide polymorphisms (SNPs) in Prkdc, the gene encoding the DNA-dependent protein kinase catalytic subunit (DNA-PKcs), have been identified in BALB/c mice and linked to reduced DNA-PKcs activity and mammary cancer susceptibility. We examined three additional mouse strains to better define the roles of the BALB/c Prkdc SNPs (R2140C and M3844V). One is a congenic strain (C.B6) that has the C57BL/6 Prkdc allele on a BALB/c background, and the other is a congenic strain (B6.C) that has the BALB/c variant Prkdc allele on a C57BL/6 background. We also examined the LEWES mouse strain, which possesses only one of the BALB/c Prkdc SNPs (M3844V). Our results demonstrate that both Prkdc SNPs are responsible for deficient DNA-PKcs protein expression, DNA repair and telomere function, while the LEWES SNP affects only DNA-PKcs expression and repair capacity. These studies provide insight into the separation of function between the two BALB/c SNPs as well as direct evidence that SNPs positioned within Prkdc can significantly influence DNA-PKcs function involving DNA repair capacity, telomere end-capping, and potentially cancer susceptibility.

Original languageEnglish (US)
Pages (from-to)493-500
Number of pages8
JournalRadiation research
Issue number4
StatePublished - Apr 1 2011

ASJC Scopus subject areas

  • Biophysics
  • Radiation
  • Radiology Nuclear Medicine and imaging

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    Fabre, K. M., Ramaiah, L., Dregalla, R. C., Desaintes, C., Weil, M. M., Bailey, S. M., & Ullrich, R. L. (2011). Murine Prkdc polymorphisms impact DNA-PKcs function. Radiation research, 175(4), 493-500.