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DNA-PK

The DNA-PK holoenzyme comprises a heterodimer of approximately 70- and 80-kDa polypeptides, known as Ku, that binds to DNA strand breaks, recruiting and activating the 470-kDa catalytic subunit, termed DNA-PKcs. Cells lacking DNA-PK are hypersensitive to IR and cross-linking agents and defective in DSB repair. DNA-PK, together with the x-ray cross complementing (XRCC4)/DNA ligase IV complex and the recently identified cofactor Artemis, is specifically required for NHEJ, with about 80% of DNA DSBs repaired by this pathway. DNA-PK can accelerate the repair of IR-, etoposide-, and doxorubicin-induced DSBs, thus conferring resistance to these agents. The inhibition of DNA-PK is an attractive approach for modulating resistance to therapeutically-induced DNA DSBs.

References

1.Furgason JM,et al. Pharmacol Ther. 2013;137(3):298–308.

Cell Cycle/DNA Damage

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