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Trapping of PARP1 and PARP2 by Clinical PARP Inhibitors.
Small-molecule inhibitors of PARP are thought to mediate their antitumor effects as catalytic inhibitors that block repair of DNA single-strand breaks (SSB). However, the mechanism of action of PARPExpand
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Roles of eukaryotic topoisomerases in transcription, replication and genomic stability
Topoisomerases introduce transient DNA breaks to relax supercoiled DNA, remove catenanes and enable chromosome segregation. Human cells encode six topoisomerases (TOP1, TOP1mt, TOP2α, TOP2β, TOP3αExpand
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Stereospecific PARP Trapping by BMN 673 and Comparison with Olaparib and Rucaparib
Anti-PARP drugs were initially developed as catalytic inhibitors to block the repair of DNA single-strand breaks. We recently reported that several PARP inhibitors have an additional cytotoxicExpand
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Tyrosyl-DNA-phosphodiesterases (TDP1 and TDP2).
TDP1 and TDP2 were discovered and named based on the fact they process 3'- and 5'-DNA ends by excising irreversible protein tyrosyl-DNA complexes involving topoisomerases I and II, respectively. Yet,Expand
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PARP1–TDP1 coupling for the repair of topoisomerase I–induced DNA damage
Poly(ADP-ribose) polymerases (PARP) attach poly(ADP-ribose) (PAR) chains to various proteins including themselves and chromatin. Topoisomerase I (Top1) regulates DNA supercoiling and is the target ofExpand
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Tyrosyl-DNA Phosphodiesterase 1 (TDP1) Repairs DNA Damage Induced by Topoisomerases I and II and Base Alkylation in Vertebrate Cells*
Background: Tdp1 is a DNA repair enzyme conserved across eukaryotes. Results: Tdp1 repairs not only 3′-tyrosyl-DNA bonds and 3′-phosphoglycolates but also 5′-tyrosyl-DNA bonds and 3′-deoxyriboseExpand
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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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Biochemical Characterization of Human Tyrosyl-DNA Phosphodiesterase 2 (TDP2/TTRAP)
Background: TDP2 is the only known tyrosine 5′-phosphodiesterase. Results: Recombinant human TDP2 preferentially processes single-stranded DNA ends. Its catalytic site is similar to APE-1 andExpand
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TDP1 repairs nuclear and mitochondrial DNA damage induced by chain-terminating anticancer and antiviral nucleoside analogs
Chain-terminating nucleoside analogs (CTNAs) that cause stalling or premature termination of DNA replication forks are widely used as anticancer and antiviral drugs. However, it is not wellExpand
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Topoisomerase I‐mediated cleavage at unrepaired ribonucleotides generates DNA double‐strand breaks
Ribonuclease activity of topoisomerase I (Top1) causes DNA nicks bearing 2′,3′‐cyclic phosphates at ribonucleotide sites. Here, we provide genetic and biochemical evidence that DNA double‐strandExpand
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