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Title: MRE11 facilitates the removal of human topoisomerase II complexes from genomic DNA
Authors: Lee, KC
Padget, K
Curtis, H
Cowell, IG
Moiani, D
Sondka, Z
Morris, NJ
Jackson, GH
Cockell, SJ
Tainer, JA
Austin, CA
Keywords: Topoisomerase II;MRE11;DSB repair;Protein-DNA adducts
Issue Date: 2012
Publisher: Published by The Company of Biologists Ltd
Citation: Biology Open, 2012, 1 (9), pp. 863 - 873
Abstract: Topoisomerase II creates a double-strand break intermediate with topoisomerase covalently coupled to the DNA via a 59phosphotyrosyl 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 IIa 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 IIa and b complex levels formed in the absence of an anti-topoisomerase II drug.
Appears in Collections:Dept of Life Sciences Research Papers

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