DNA topoisomerase III alpha regulates p53-mediated tumor suppression

Mei-Yi Hsieh1, Jia-Rong Fan, Han-Wen Chang

  • 1Authors' Affiliations: Department and Graduate Institute of Microbiology, College of Medicine, Department of Plan Pathology and Microbiology, College of Bioresources and Agriculture, and Center for Biotechnology, National Taiwan University, Taipei, Taiwan.

Abstract

Insights

Human DNA topoisomerase III alpha (hTOP3α) interacts with p53, regulating its expression and acting as a tumor suppressor. Loss of hTOP3α promotes cancer growth, highlighting its role in DNA repair and cell cycle control.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Biochemistry

Background:

  • Human DNA topoisomerase III alpha (hTOP3α) is implicated in DNA repair and cell-cycle checkpoints, potentially via complexes with tumor suppressors.
  • The precise role of hTOP3α in cancer development remains largely uncharacterized.

Purpose of the Study:

  • To investigate the interaction between hTOP3α and p53.
  • To elucidate the role of hTOP3α in cancer development and its underlying molecular mechanisms.

Main Methods:

  • Coimmunoprecipitation, sucrose gradient, chromatin immunoprecipitation (ChIP), real-time PCR, and immunoblotting were used to study hTOP3α-p53 interactions.
  • Cell lines with varying hTOP3α levels were created using ectopic expression and shRNA knockdown.
  • Tumorigenic properties were assessed via cell counting, colony formation, senescence, soft agar assays, and mouse xenografts.

Main Results:

  • hTOP3α directly binds to p53 and positively regulates the expression of p53 and p21.
  • Knockdown of hTOP3α increased tumorigenicity in non-tumorigenic cells and altered it in cancer cell lines.
  • Functional hTOP3α, p53, and p21 are essential for tumor suppression, with both proteins influencing each other's promoter recruitment.

Conclusions:

  • hTOP3α interacts with p53 and modulates p53 and p21 expression.
  • hTOP3α functions as a tumor suppressor by contributing to p53-mediated pathways.

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