MRE11 facilitates the removal of human topoisomerase II complexes from genomic DNA

Ka Cheong Lee, Kay Padget, Hannah Curtis, Ian Cowell, Davide Moiani, Zbyslaw Sondka, Nicholas Morris, Graham Jackson, Simon Cockell, John Tainer, Caroline Austin

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37 Citations (Scopus)
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Abstract

Topoisomerase II creates a double-strand break intermediate with topoisomerase covalently coupled to the DNA via a 5'-phosphotyrosyl bond. These intermediate complexes can become cytotoxic protein-DNA adducts and DSB repair at these lesions requires removal of topoisomerase II. To analyse removal of topoisomerase II from genomic DNA we adapted the trapped in agarose DNA immunostaining assay. Recombinant MRE11 from 2 sources removed topoisomerase IIalpha from genomic DNA in vitro, as did MRE11 immunoprecipitates isolated from A-TLD or K562 cells. Basal topoisomerase II complex levels were very high in A-TLD cells lacking full-length wild type MRE11, suggesting that MRE11 facilitates the processing of topoisomerase complexes that arise as part of normal cellular metabolism. In K562 cells inhibition of MRE11, PARP or replication increased topoisomerase IIalpha and beta complex levels formed in the absence of an anti-topoisomerase II drug
Original languageEnglish
Pages (from-to)863-873
JournalBiology Open
Volume1
Issue number9
DOIs
Publication statusPublished - 2012

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