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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, PADNA-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.
History
Publication title
National Academy of Sciences of The United States of America. ProceedingsVolume
93Issue
19Pagination
10285-10290ISSN
0027-8424Department/School
Menzies Institute for Medical ResearchPublisher
Natl Acad SciencesPlace of publication
2101 Constitution Ave Nw, Washington, USA, Dc, 20418Repository Status
- Restricted