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  • Title: Threonines 2638/2647 in DNA-PK are essential for cellular resistance to ionizing radiation.
    Author: Soubeyrand S, Pope L, Pakuts B, Haché RJ.
    Journal: Cancer Res; 2003 Mar 15; 63(6):1198-201. PubMed ID: 12649176.
    Abstract:
    DNA-dependent protein kinase (DNA-PK) is required for the repair of double-stranded DNA breaks through the nonhomologous DNA end joining pathway. DNA-PK activity is required for DNA repair, but kinase activity also appears to be attenuated through an autoregulatory feedback loop. We show that autophosphorylation of DNA-PK catalytic subunit occurs in trans at least three sites NH(2) terminal to the catalytic domain and that two sites, threonine 2638 and 2647, determine DNA-PK autophosphorylation in vitro. Thr2638/2647ala substitution in DNA-PK catalytic subunit compromised cellular resistance to ionizing radiation without affecting DNA end joining, suggesting a requirement for DNA-PK inactivation for cell survival at a step after the rejoining of double-stranded DNA breaks.
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