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Reversal of DNA damage induced Topoisomerase 2 DNA-protein crosslinks by Tdp2.

Nucleic acids research - 5 May 2016

Schellenberg Matthew J, Perera Lalith, Strom Christina N, Waters Crystal A, Monian Brinda, Appel C Denise, Vilas Caroline K, Williams Jason G, Ramsden Dale A, Williams R Scott

Abstract excerpt

Mammalian Tyrosyl-DNA phosphodiesterase 2 (Tdp2) reverses Topoisomerase 2 (Top2) DNA-protein crosslinks triggered by Top2 engagement of DNA damage or poisoning by anticancer drugs. Tdp2 deficiencies are linked to neurological disease and cellular sensitivity to Top2 poisons. Herein, we report X-ray crystal structures of ligand-free Tdp2 and Tdp2-DNA complexes with alkylated and abasic DNA that unveil a dynamic...

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PMID: 27060144
DOI: 10.1093/nar/gkw228
PMCID: PMC4857006

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