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Updated: May 24, 2025

Studying RNA Interactors of Protein Kinase RNA-Activated during the Mammalian Cell Cycle
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Studying RNA Interactors of Protein Kinase RNA-Activated during the Mammalian Cell Cycle

Published on: March 5, 2019

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DNA-PKcs, a player winding and dancing with RNA metabolism and diseases

Jiabao Hou1, Mingjun Lu1, Jingwei Guo1

  • 1Cancer Research Center, Beijing Chest Hospital, Beijing Tuberculosis and Thoracic Tumor Research Institute, Capital Medical University, Beijing, 101149, China.

Cellular & Molecular Biology Letters
|March 4, 2025
PubMed

Insights

DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is crucial for DNA repair but also implicated in tumor progression. This review explores its non-DNA repair roles in RNA metabolism, offering new therapeutic targets.

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Biochemistry

Background:

  • DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is a critical enzyme in DNA repair pathways, maintaining genomic stability.
  • Overexpression of DNA-PKcs in solid tumors correlates with poor prognosis, highlighting its oncogenic potential.
  • Initially recognized for DNA repair, DNA-PKcs exhibits diverse non-canonical functions.

Purpose of the Study:

  • To review the multifaceted roles of DNA-PKcs in RNA metabolism.
  • To elucidate DNA-PKcs's influence on transcriptional machinery, alternative splicing, and noncoding RNA interactions.
  • To explore DNA-PKcs's non-DNA damage repair functions in the context of cancer.

Main Methods:

  • Literature review of studies on DNA-PKcs.
  • Analysis of DNA-PKcs's involvement in transcriptional regulation.
  • Examination of DNA-PKcs's impact on RNA processing and noncoding RNAs.

Main Results:

  • DNA-PKcs significantly impacts RNA metabolism, affecting transcription and alternative splicing.
  • DNA-PKcs interacts with noncoding RNAs, suggesting novel regulatory mechanisms.
  • Non-DNA repair functions of DNA-PKcs are increasingly recognized in tumorigenesis.

Conclusions:

  • DNA-PKcs possesses pleiotropic roles beyond DNA repair, including critical functions in RNA metabolism.
  • Targeting DNA-PKcs pharmacologically may offer a promising therapeutic strategy for various cancers.
  • Further research into DNA-PKcs's non-canonical functions can uncover new avenues for cancer treatment.
Keywords:
Alternative splicingDNA-PKcsNoncoding RNAsRNA metabolismTranscriptional regulation

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