The DNA-dependent protein kinase (DNA-PK) is a pivotal component of the DNA repair machinery that governs the response to DNA damage, serving to maintain genome integrity. However, the DNA-PK kinase component was initially isolated with transcriptional complexes, and recent fi ndings have illuminated the impact of DNA-PK–mediated transcriptional regulation on tumor progression and therapeutic response. DNA-PK expression has also been correlated with poor outcome in selected tumor types, further underscoring the importance of understanding its role in disease. Herein, the molecular and cellular consequences of DNA-PK are considered, with an eye toward discerning the rationale for therapeutic targeting of DNA-PK. Significance: Although DNA-PK is classically considered a component of damage response, recent fi ndings illuminate damage-independent functions of DNA-PK that affect multiple tumor-associated pathways and provide a rationale for the development of novel therapeutic strategies.
CITATION STYLE
Goodwin, J. F., & Knudsen, K. E. (2014). Beyond DNA repair: DNA-PK function in cancer. Cancer Discovery, 4(10), 1126–1139. https://doi.org/10.1158/2159-8290.CD-14-0358
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