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Biochimie. 1999 Jan-Feb;81(1-2):117-25.

Regulation of the DNA-dependent protein kinase (DNA-PK) activity in eukaryotic cells.

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Institut de Pharmacologie et de Biologie Structurale, CNRS, UPR 906, Toulouse, France.


The DNA-dependent protein kinase (DNA-PK) is a trimeric nuclear serine/threonine protein kinase consisting of a large catalytic sub-unit and the Ku heterodimer that regulates kinase activity by its association with DNA. DNA-PK is a major component of the DNA double strand break repair apparatus, and cells deficient in one of its component are hypersensitive to ionizing radiation. DNA-PK is also required to lymphoid V(D)J recombination and its absence confers in mice a severe combined immunodeficiency phenotype. The purpose of this review is to summarize the current knowledge on the mechanisms that contribute to regulate DNA-PK activity in vivo or in vitro and relates them to the role of DNA-PK in cellular functions. Finally, the studies devoted to drug-inhibition of DNA-PK in order to enhance cancer therapy by DNA-damaging agents are presented.

[Indexed for MEDLINE]

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