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

Lee, Ka Cheong, Padget, Kay, Curtis, Hannah, Cowell, Ian, Moiani, Davide, Sondka, Zbyslaw, Morris, Nicholas, Jackson, Graham, Cockell, Simon, Tainer, John and Austin, Caroline (2012) MRE11 facilitates the removal of human topoisomerase II complexes from genomic DNA. Biology Open, 1 (9). pp. 863-873. ISSN 2046-6390

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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

Item Type: Article
Additional Information: Funding information: This work was funded by LRF grant 04037 and LLR grant 07038 (K.C.L., K.P., H.C., I.G.C., Z.S., G.H.J., N.J.M., S.J.C. and C.A.A.). The efforts of D.M. and J.A.T. on Mre11 mutant preparations were supported by National Cancer Institute grant CA117638 (J.A.T.).
Uncontrolled Keywords: Topoisomerase II, MRE11, DSB repair, Protein-DNA adducts, A-TLD
Subjects: C700 Molecular Biology, Biophysics and Biochemistry
Department: Faculties > Health and Life Sciences > Applied Sciences
Depositing User: Linda Barlow
Date Deposited: 30 Jan 2013 15:44
Last Modified: 17 Dec 2023 14:01

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