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Simple and Fast Rolling Circle Amplification-Based Detection of Topoisomerase 1 Activity in Crude Biological Samples

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Topoisomerase Regulation of Cancer Gene Expression.

Laura Baranello¹, Fedor Kouzine², David Levens²

¹Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden;

Annual Review of Biochemistry

|March 18, 2025

Summary

Cancer cells manage DNA mechanical stress using topoisomerases. When this stress overwhelms topoisomerase capacity, DNA damage occurs, promoting cancer progression.

Keywords:

DNA topology MYC cancer non-B DNA topoisomerase transcription

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Published on: March 30, 2019

Area of Science:

Genomics
Molecular Biology
Cancer Biology

Background:

Hyperproliferative conditions in cancer elevate DNA mechanical stress.
Topoisomerases are crucial enzymes that manage DNA topology and regulate genomic processes.
Dysregulation of topoisomerase activity is implicated in cancer development and progression.

Purpose of the Study:

To summarize the critical roles of topoisomerases in cancer.
To highlight how topoisomerases manage oncogene-driven genomic stress.
To elucidate the mechanisms by which topoisomerase failure contributes to tumorigenesis.

Main Methods:

Literature review of topoisomerase functions in cancer.
Analysis of DNA topological stress and its management by topoisomerases.
Examination of aberrant DNA structures arising from topoisomerase dysfunction.

Main Results:

Topoisomerases regulate transcription, replication, and chromatin transactions in cancer cells.
Exceeding topoisomerase capacity leads to R-loop formation and transcription-replication conflicts.
Topoisomerase catalytic failure results in topological dysregulation and DNA damage, fueling tumorigenesis.

Conclusions:

Topoisomerases are essential for maintaining genomic stability under hyperproliferative conditions.
Impaired topoisomerase function is a significant driver of DNA damage and cancer progression.
Understanding cancer-specific topoisomerase roles is vital for developing targeted therapies.