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 Citations (Scopus)

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 2011

Fingerprint

DNA-Activated Protein Kinase
polymorphism
nucleotides
Single Nucleotide Polymorphism
Catalytic Domain
deoxyribonucleic acid
proteins
DNA Repair
telomeres
mice
Telomere
genes
Alleles
cancer
magnetic permeability
Ionizing Radiation
Genes
ionizing radiation
catalytic activity
coding

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Biophysics
  • Radiation

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

Murine Prkdc polymorphisms impact DNA-PKcs function. / Fabre, Kristin M.; Ramaiah, Lila; Dregalla, Ryan C.; Desaintes, Christian; Weil, Michael M.; Bailey, Susan M.; Ullrich, Robert L.

In: Radiation Research, Vol. 175, No. 4, 04.2011, p. 493-500.

Research output: Contribution to journalArticle

Fabre, KM, Ramaiah, L, Dregalla, RC, Desaintes, C, Weil, MM, Bailey, SM & Ullrich, RL 2011, 'Murine Prkdc polymorphisms impact DNA-PKcs function', Radiation Research, vol. 175, no. 4, pp. 493-500. https://doi.org/10.1667/RR2431.1
Fabre KM, Ramaiah L, Dregalla RC, Desaintes C, Weil MM, Bailey SM et al. Murine Prkdc polymorphisms impact DNA-PKcs function. Radiation Research. 2011 Apr;175(4):493-500. https://doi.org/10.1667/RR2431.1
Fabre, Kristin M. ; Ramaiah, Lila ; Dregalla, Ryan C. ; Desaintes, Christian ; Weil, Michael M. ; Bailey, Susan M. ; Ullrich, Robert L. / Murine Prkdc polymorphisms impact DNA-PKcs function. In: Radiation Research. 2011 ; Vol. 175, No. 4. pp. 493-500.
@article{7cc430dea32c408e8c095399a8e6c9e1,
title = "Murine Prkdc polymorphisms impact DNA-PKcs function",
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.",
author = "Fabre, {Kristin M.} and Lila Ramaiah and Dregalla, {Ryan C.} and Christian Desaintes and Weil, {Michael M.} and Bailey, {Susan M.} and Ullrich, {Robert L.}",
year = "2011",
month = "4",
doi = "10.1667/RR2431.1",
language = "English (US)",
volume = "175",
pages = "493--500",
journal = "Radiation Research",
issn = "0033-7587",
publisher = "Radiation Research Society",
number = "4",

}

TY - JOUR

T1 - Murine Prkdc polymorphisms impact DNA-PKcs function

AU - Fabre, Kristin M.

AU - Ramaiah, Lila

AU - Dregalla, Ryan C.

AU - Desaintes, Christian

AU - Weil, Michael M.

AU - Bailey, Susan M.

AU - Ullrich, Robert L.

PY - 2011/4

Y1 - 2011/4

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=79953329983&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79953329983&partnerID=8YFLogxK

U2 - 10.1667/RR2431.1

DO - 10.1667/RR2431.1

M3 - Article

C2 - 21265624

AN - SCOPUS:79953329983

VL - 175

SP - 493

EP - 500

JO - Radiation Research

JF - Radiation Research

SN - 0033-7587

IS - 4

ER -