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Nucleotide Excision Repair01:38

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Aurora-A: a potential DNA repair modulator.

Yan Wang1, Huizhen Sun, Ziliang Wang

  • 1Cancer Institute, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, China, wangxyyan@sina.com.

Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine
|November 27, 2013
PubMed
Summary

Aurora-A overexpression promotes cancer. This review explores its role in DNA repair, showing it modulates cancer cell sensitivity to chemotherapy and radiation, suggesting Aurora-A targets for therapy.

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Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Overexpression of Aurora-A kinase is linked to tumorigenesis.
  • Its precise role in cancer development, particularly in chemo- and radioresistance, requires further investigation.
  • Aurora-A influences cell cycle progression and DNA damage response pathways.

Purpose of the Study:

  • To review and summarize the current literature on the role of Aurora-A in DNA repair.
  • To elucidate the mechanisms by which Aurora-A affects cancer cell sensitivity to therapeutic agents.
  • To identify potential therapeutic targets associated with Aurora-A in cancer treatment.

Main Methods:

  • Literature review of existing studies on Aurora-A.
  • Analysis of Aurora-A's interactions with cell cycle regulators (e.g., pRb, p53, CDK1, cyclin B1).
  • Examination of Aurora-A's impact on DNA damage response proteins (e.g., BRCA1, BRCA2, PARP, gamma-H2AX).

Main Results:

  • Aurora-A dysregulates cell cycle checkpoints by inhibiting inhibitors (pRb, p53, p21, p27) and enhancing activators (Plk1, CDC25, CDK1, cyclin B1).
  • Aurora-A suppresses key DNA repair proteins including BRCA1, BRCA2, RAD51, PARP, and gamma-H2AX, thereby impairing DNA damage response.
  • Evidence suggests Aurora-A indirectly influences DNA repair through interactions with RAS and Myc.

Conclusions:

  • Aurora-A acts as a modulator of DNA repair processes in cancer cells.
  • Its activity influences cancer cell radio- and chemosensitivity.
  • Aurora-A-associated DNA repair molecules represent promising targets for novel cancer therapies.