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Tyrosyl-DNA phosphodiesterase (Tdp1) participates in the repair of Top2-mediated DNA damage.
Agents targeting topoisomerases are active against a wide range of human tumors. Stabilization of covalent complexes, converting topoisomerases into DNA-damaging agents, is an essential aspect ofExpand
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A Novel Mechanism of Cell Killing by Anti-topoisomerase II Bisdioxopiperazines*
Bisdioxopiperazines are a unique class of topoisomerase II inhibitors that lock topoisomerase II at a point in the enzyme reaction cycle where the enzyme forms a closed clamp around DNA. We examinedExpand
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Proteolytic Degradation of Topoisomerase II (Top2) Enables the Processing of Top2·DNA and Top2·RNA Covalent Complexes by Tyrosyl-DNA-Phosphodiesterase 2 (TDP2)* ♦
Background: TDP2 is critical for repairing Top2 cleavage complexes (Top2cc) and as the VPg unlinkase for picornavirus replication. Results: Top2 proteolysis or denaturation is required for TDP2Expand
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Aberrant Topoisomerase-1-DNA Lesions are Pathogenic in Neurodegenerative Genome Instability Syndromes
DNA damage is considered to be a prime factor in several spinocerebellar neurodegenerative diseases; however, the DNA lesions underpinning disease etiology are unknown. We observed the endogenousExpand
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Yeast Tdp1 regulates the fidelity of nonhomologous end joining
Tyrosyl-DNA-phosphodiesterase 1 (Tdp1) can disjoin peptides covalently bound to DNA. We assessed the role of Tdp1 in nonhomologous end joining (NHEJ) and found that linear DNA molecules with 5′Expand
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Yeast recombination pathways triggered by topoisomerase II-mediated DNA breaks.
Topoisomerase II is a ubiquitous enzyme that removes knots and tangles from the genetic material by generating transient double-strand DNA breaks. While the enzyme cannot perform its essentialExpand
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TDP1 promotes assembly of non-homologous end joining protein complexes on DNA.
The repair of DNA double-strand breaks (DSB) is central to the maintenance of genomic integrity. In tumor cells, the ability to repair DSBs predicts response to radiation and many cytotoxicExpand
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Enhancing Drug Accumulation in Saccharomyces cerevisiae by Repression of Pleiotropic Drug Resistance Genes with Chimeric Transcription Repressors
Yeast is a powerful model system for studying the action of small-molecule therapeutics. An important limitation has been low efficacy of many small molecules in yeast due to limited intracellularExpand
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Roles of nonhomologous end-joining pathways in surviving topoisomerase II–mediated DNA damage
Topoisomerase II is a target for clinically active anticancer drugs. Drugs targeting these enzymes act by preventing the religation of enzyme-DNA covalent complexes leading to protein-DNA adductsExpand
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Mutation of a conserved active site residue converts tyrosyl-DNA phosphodiesterase I into a DNA topoisomerase I-dependent poison.
Tyrosyl-DNA phosphodiesterase 1 (Tdp1) catalyzes the resolution of 3' and 5' phospho-DNA adducts. A defective mutant, associated with the recessive neurodegenerative disease SCAN1, accumulatesExpand
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