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Updated: Aug 12, 2026

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Genetic Studies of Human DNA Repair Proteins Using Yeast as a Model System
Published on: March 18, 2010
Human TOP3: a single-copy gene encoding DNA topoisomerase III
1Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02139, USA.
Summary
Researchers identified a human gene, TOP3, encoding DNA topoisomerase III. This enzyme, when expressed in yeast, effectively reduces DNA supercoiling, suggesting a crucial role in DNA replication and repair.
Area of Science:
- Molecular Biology
- Genetics
- Biochemistry
Background:
- DNA topoisomerases are essential enzymes involved in managing DNA topology.
- Understanding human DNA topoisomerase III (TOP3) function is critical for comprehending DNA replication and repair mechanisms.
Purpose of the Study:
- To identify and characterize the human gene encoding DNA topoisomerase III.
- To confirm the enzymatic activity of the human TOP3 protein.
Main Methods:
- Human cDNA cloning and sequencing.
- Expression of human TOP3 in yeast (delta)top1 mutant cells.
- Assay of DNA topoisomerase activity in cell extracts.
- Human gene localization using somatic hybrid panels and fluorescence in situ hybridization (FISH).
Main Results:
- A human cDNA homologous to E. coli DNA topoisomerase I was identified and sequenced.
- The expressed human protein demonstrated specific activity in reducing DNA supercoiling.
- The human gene was designated TOP3, and the protein DNA topoisomerase III.
- TOP3 was localized to chromosome 17p11.2-12 as a single-copy gene.
Conclusions:
- The human TOP3 gene encodes a functional DNA topoisomerase III enzyme.
- TOP3 plays a significant role in DNA topology regulation.
- The precise chromosomal location of TOP3 provides a basis for further genetic studies.
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