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. 1997 Mar;17(3):1425-33.
doi: 10.1128/MCB.17.3.1425.

Evidence for DNA-PK-dependent and -independent DNA double-strand break repair pathways in mammalian cells as a function of the cell cycle

S E Lee  1 , R A Mitchell, A Cheng, E A Hendrickson
Affiliations

Evidence for DNA-PK-dependent and -independent DNA double-strand break repair pathways in mammalian cells as a function of the cell cycle

S E Lee et al. Mol Cell Biol. 1997 Mar.

Abstract

Mice homozygous for the scid (severe combined immune deficiency) mutation are defective in the repair of DNA double-strand breaks (DSBs) and are consequently very X-ray sensitive and defective in the lymphoid V(D)J recombination process. Recently, a strong candidate for the scid gene has been identified as the catalytic subunit of the DNA-dependent protein kinase (DNA-PK) complex. Here, we show that the activity of the DNA-PK complex is regulated in a cell cycle-dependent manner, with peaks of activity found at the G1/early S phase and again at the G2 phase in wild-type cells. Interestingly, only the deficit of the G1/early S phase DNA-PK activity correlated with an increased hypersensitivity to X-irradiation and a DNA DSB repair deficit in synchronized scid pre-B cells. Finally, we demonstrate that the DNA-PK activity found at the G2 phase may be required for exit from a DNA damage-induced G2 checkpoint arrest. These observations suggest the presence of two pathways (DNA-PK-dependent and -independent) of illegitimate mammalian DNA DSB repair and two distinct roles (DNA DSB repair and G2 checkpoint traversal) for DNA-PK in the cellular response to ionizing radiation.

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References

    1. J Biol Chem. 1996 Jun 14;271(24):14098-104 - PubMed
    1. Mol Cell Biol. 1996 Aug;16(8):4189-98 - PubMed
    1. Nature. 1996 Aug 8;382(6591):551-5 - PubMed
    1. Genetics. 1996 Jan;142(1):91-102 - PubMed
    1. Proc Natl Acad Sci U S A. 1994 Dec 20;91(26):12520-4 - PubMed

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