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Exploration of the Role of the C-Terminal Domain of Human DNA Topoisomerase IIα in Catalytic Activity

ACS Omega. 2021-09; 
Ashley C Dougherty, Mariam G Hawaz, Kristine G Hoang, Judy Trac, Jacob M Keck, Carmen Ayes, Joseph E Deweese
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Mutagenesis Services … Synthesis and sequencing of the construct were carried out by GenScript (Piscataway, NJ). Mutant enzymes were designed to remove Ser … Mutagenesis and sequencing to validate changes were carried out by GenScript (Piscataway, NJ). Sequencing data are available upon … Get A Quote

摘要

Human topoisomerase IIα (TOP2A) is a vital nuclear enzyme involved in resolving knots and tangles in DNA during replication and cell division. TOP2A is a homodimer with a symmetrical, multidomain structure. While the N-terminal and core regions of the protein are well-studied, the C-terminal domain is poorly understood but is involved in enzyme regulation and is predicted to be intrinsically disordered. In addition, it appears to be a major region of post-translational modification and includes several Ser and Thr residues, many of which have not been studied for biochemical effects. Therefore, we generated a series of human TOP2A mutants where we changed specific Ser and Thr residues in the C-terminal domain ... More

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