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Identification of a nonsense mutation in the carboxyl-terminal region of DNA-dependent protein kinase catalytic subunit in the scid mouse

journal contribution
posted on 2023-05-17, 03:00 authored by Blunt, T, David GellDavid Gell, Fox, M, Taccioli, GE, Lehmann, AR, Jackson, SP, Jeggo, PA
DNA-dependent protein kinase (DNA-PK) consists of a heterodimeric protein (Ku) and a large catalytic subunit (DNA-PKcs). The Ku protein has double-stranded DNA end-binding activity that serves to recruit the complex to DNA ends. Despite having serine/threonine protein kinase activity, DNA- PKcs falls into the phosphatidylinositol 3-kinase superfamily. DNA. PK functions in DNA double-strand break repair and V(D)J recombination, and recent evidence has shown that mouse scid cells are defective in DNA-PKcs. In this study we have cloned the cDNA for the carboxyl-terminal region of DNA- PKcs in rodent cells and identifed the existence of two differently spliced products in human cells. We show that DNA-PKcs maps to the same chromosomal region as the mouse scid gene, scid cells contain approximately wild-type levels of DNA-PKcs transcripts, whereas the V-3 cell line, which is also defective in DNA-PKcs, contains very reduced transcript levels. Sequence comparison of the carboxyl-terminal region of scid and wild-type mouse cells enabled us to identify a nonsense mutation within a highly conserved region of the gene in mouse scid cells. This represents a strong candidate for the inactivating mutation in DNA-PKcs in the scid mouse.


Publication title

National Academy of Sciences of The United States of America. Proceedings










Menzies Institute for Medical Research


Natl Acad Sciences

Place of publication

2101 Constitution Ave Nw, Washington, USA, Dc, 20418

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Expanding knowledge in the biological sciences

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