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Topoisomerase IIIα resolves inter- and intra-molecular intertwines during DNA replication
Biorxiv : the Preprint Server for Biology
|July 10, 2026
Summary
Topoisomerase IIIα (TOP3α) is vital for genome integrity, especially when Topoisomerase IIα (TOP2α) is impaired. TOP3α resolves DNA linkages during replication termination and when single-stranded DNA levels rise, ensuring genome stability.
Area of Science:
- Molecular Biology
- Genetics
- Biochemistry
Background:
- Genome integrity relies on resolving topological stress.
- Vertebrate topoisomerase IIα (TOP2α) resolves catenanes during DNA replication.
- The role of Topoisomerase IIIα (TOP3α) in DNA replication is not fully understood.
Purpose of the Study:
- To investigate the role of TOP3α in DNA replication, particularly when TOP2α function is compromised.
- To determine TOP3α's substrate specificity and binding partners during replication.
Main Methods:
- Utilized Xenopus egg extracts for in vitro DNA replication studies.
- Assessed replication fork progression and daughter strand unlinking.
- Investigated TOP3α activity independently of RMI1-RMI2 and BLM helicase.
Main Results:
- TOP3α promotes replication fork progression and daughter strand unlinking during replication termination.
- TOP3α acts on lagging-strand single-stranded DNA (ssDNA) independently of known partners.
- Elevated lagging-strand ssDNA leads to intramolecular ssDNA intertwines resolved by TOP3α.
Conclusions:
- TOP3α is essential for resolving DNA topological stress during replication termination.
- TOP3α resolves both intermolecular and intramolecular DNA linkages, crucial for genome stability under various replication conditions.
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