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Untangling the roles of TOP2A and TOP2B in transcription and cancer

Liis Uusküla-Reimand1, Michael D Wilson1,2

  • 1Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON, Canada.

Science Advances
|November 2, 2022
PubMed

Insights

Type II topoisomerases (TOP2) manage DNA topology by creating temporary breaks, crucial for cell processes but also linked to cancer. This review explores TOP2A and TOP2B roles in chromatin regulation and cancer development.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cancer Research

Background:

  • Type II topoisomerases (TOP2) are essential enzymes that regulate DNA topology.
  • They function by catalyzing reversible DNA double-strand breaks (DSBs), critical for transcription, replication, and cell division.
  • While vital for genomic integrity, TOP2-mediated DSBs can lead to mutations and chromosomal translocations, contributing to cancer.

Purpose of the Study:

  • To provide an updated overview of TOP2A and TOP2B functions.
  • To discuss the role of TOP2 enzymes in chromatin topology and transcription.
  • To explore recent findings linking TOP2 activities to cancer pathogenesis.

Main Methods:

  • Literature review of recent discoveries.
  • Analysis of TOP2A and TOP2B roles in cellular processes.
  • Synthesis of information on TOP2 and cancer development.

Main Results:

  • TOP2 enzymes are crucial for managing DNA topological constraints during essential cellular activities.
  • Dysregulation of TOP2 activity and resulting DNA breaks are implicated in genomic instability and cancer.
  • Specific roles of TOP2A and TOP2B in transcription and chromatin structure are highlighted.

Conclusions:

  • TOP2 enzymes play a dual role in maintaining genomic stability and potentially driving cancer.
  • Understanding TOP2A and TOP2B functions is critical for cancer biology and therapeutic strategies.
  • Further research is needed to fully elucidate the precise mechanisms linking TOP2 activity to cancer pathogenesis.

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