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Beyond DNA repair: DNA-PK function in cancer.

By Jonathan F Goodwin and Karen E Knudsen

Abstract

UNLABELLED: 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 findings 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 findings illuminate damage-independent functions of DNA-PK that affect multiple tumor-associated pathways and provide a rationale for the development of novel therapeutic strategies

Topics: Kimmel Cancer Center, Department of Radiation Oncology, Department of Urology, Department of Cancer Biology, Thomas Jefferson University; Article; autoregulation; carcinogenesis; DNA end joining repair; drug targeting; gene mutation; gene rearrangement; genomic instability; homologous recombination; human; hypoxia; inflammation; innate immunity; neoplasm; nonhuman; protein expression; protein phosphorylation; signal transduction, Oncology
Publisher: Jefferson Digital Commons
Year: 2014
OAI identifier: oai:jdc.jefferson.edu:radoncfp-1060

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