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Restoration of ATM Expression in DNA-PKcs-Deficient Cells Inhibits Signal End Joining.
Neal, Jessica A; Xu, Yao; Abe, Masumi; Hendrickson, Eric; Meek, Katheryn.
Afiliação
  • Neal JA; Department of Microbiology and Molecular Genetics, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824; Department of Pathobiology and Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824;
  • Xu Y; Department of Microbiology and Molecular Genetics, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824; Department of Pathobiology and Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824;
  • Abe M; National Institute of Radiological Sciences, Chiba 263-8555, Japan; and.
  • Hendrickson E; Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota Medical School, Minneapolis, MN 55455.
  • Meek K; Department of Microbiology and Molecular Genetics, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824; Department of Pathobiology and Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824; kmeek@msu.edu.
J Immunol ; 196(7): 3032-42, 2016 Apr 01.
Article em En | MEDLINE | ID: mdl-26921311
Unlike most DNA-dependent protein kinase, catalytic subunit (DNA-PKcs)-deficient mouse cell strains, we show in the present study that targeted deletion of DNA-PKcs in two different human cell lines abrogates VDJ signal end joining in episomal assays. Although the mechanism is not well defined, DNA-PKcs deficiency results in spontaneous reduction of ATM expression in many cultured cell lines (including those examined in this study) and in DNA-PKcs-deficient mice. We considered that varying loss of ATM expression might explain differences in signal end joining in different cell strains and animal models, and we investigated the impact of ATM and/or DNA-PKcs loss on VDJ recombination in cultured human and rodent cell strains. To our surprise, in DNA-PKcs-deficient mouse cell strains that are proficient in signal end joining, restoration of ATM expression markedly inhibits signal end joining. In contrast, in DNA-PKcs-deficient cells that are deficient in signal end joining, complete loss of ATM enhances signal (but not coding) joint formation. We propose that ATM facilitates restriction of signal ends to the classical nonhomologous end-joining pathway.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Expressão Gênica / Proteína Quinase Ativada por DNA / Reparo do DNA por Junção de Extremidades / Recombinação V(D)J / Proteínas Mutadas de Ataxia Telangiectasia Limite: Animals / Humans Idioma: En Ano de publicação: 2016 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Expressão Gênica / Proteína Quinase Ativada por DNA / Reparo do DNA por Junção de Extremidades / Recombinação V(D)J / Proteínas Mutadas de Ataxia Telangiectasia Limite: Animals / Humans Idioma: En Ano de publicação: 2016 Tipo de documento: Article