Restoration of ATM expression in DNA-PKcs-deficient cells inhibits signal end joining

Jessica A. Neal, Yao Xu, Masumi Abe, Eric Hendrickson, Katheryn Meek

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

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 deficency 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 DNAPKcs-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 endjoining pathway.

Original languageEnglish (US)
Pages (from-to)3032-3042
Number of pages11
JournalJournal of Immunology
Volume196
Issue number7
DOIs
StatePublished - Apr 1 2016

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DNA-Activated Protein Kinase
Catalytic Domain
V(D)J Recombination
Cell Line
Cultured Cells
Rodentia
Animal Models
Joints

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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.

In: Journal of Immunology, Vol. 196, No. 7, 01.04.2016, p. 3032-3042.

Research output: Contribution to journalArticle

Neal, Jessica A. ; Xu, Yao ; Abe, Masumi ; Hendrickson, Eric ; Meek, Katheryn. / Restoration of ATM expression in DNA-PKcs-deficient cells inhibits signal end joining. In: Journal of Immunology. 2016 ; Vol. 196, No. 7. pp. 3032-3042.
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