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

Abstract

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
Volume175
Issue number4
DOIs
StatePublished - Apr 1 2011

ASJC Scopus subject areas

  • Biophysics
  • Radiation
  • Radiology Nuclear Medicine and imaging

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  • Cite this

    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. https://doi.org/10.1667/RR2431.1