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

Lookup NU author(s): Dr Kay Padget, Hannah Curtis, Dr Ian Cowell, Dr Zbyslaw Sondka, Dr Nick Morris, Professor Graham Jackson, Dr Simon Cockell, Professor Caroline Austin

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Abstract

Topoisomerase II creates a double-strand break intermediate with topoisomerase covalently coupled to the DNA via a 59-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 II a 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 II a and b complex levels formed in the absence of an anti-topoisomerase II drug.


Publication metadata

Author(s): Lee KC, Padget K, Curtis Hannah, Cowell IG, Moiani D, Sondka Z, Morris NK, Jackson GH, Cockell SJ, Tainer JA, Austin CA

Publication type: Article

Publication status: Published

Journal: Biology Open

Year: 2012

Volume: 1

Issue: 9

Pages: 863-873

Online publication date: 16/07/2012

Date deposited: 25/04/2016

ISSN (electronic): 2046-6390

Publisher: The Company of Biologists Ltd.

URL: http://dx.doi.org/10.1242/bio.20121834

DOI: 10.1242/bio.20121834


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