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2014 ; 4
(10
): 1126-39
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Beyond DNA repair: DNA-PK function in cancer
#MMPMID25168287
Goodwin JF
; Knudsen KE
Cancer Discov
2014[Oct]; 4
(10
): 1126-39
PMID25168287
show ga
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.
|*DNA Repair
[MESH]
|Animals
[MESH]
|DNA Damage
[MESH]
|DNA-Activated Protein Kinase/antagonists & inhibitors/*metabolism
[MESH]
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