Title

Beyond DNA repair: DNA-PK function in cancer.

Document Type

Article

Publication Date

10-1-2014

Comments

This article has been peer reviewed. It was published in: Cancer Discovery.
Volume 4, Issue 10, 1 October 2014, Pages 1126-1139.
The published version is available at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4184981/

Copyright © 2014 American Association for Cancer Research.

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.