Distinct requirements for the Rad32(Mre¹¹) nuclease and Ctp1(CtIP) in the removal of covalently bound topoisomerase I and II from DNA

Hartsuiker, Edgar, Neale, Matthew J and Carr, Antony M (2009) Distinct requirements for the Rad32(Mre¹¹) nuclease and Ctp1(CtIP) in the removal of covalently bound topoisomerase I and II from DNA. Molecular Cell, 33 (1). pp. 117-123. ISSN 1097-2765

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Abstract

For a cancer cell to resist treatment with drugs that trap topoisomerases covalently on the DNA, the topoisomerase must be removed. In this study, we provide evidence that the Schizosaccharomyces pombe Rad32Mre11 nuclease activity is involved in the removal of both Top2 from 5′ DNA ends as well as Top1 from 3′ ends in vivo. A ctp1CtIP deletion is defective for Top2 removal but overproficient for Top1 removal, suggesting that Ctp1CtIP plays distinct roles in removing topoisomerases from 5′ and 3′ DNA ends. Analysis of separation of function mutants suggests that MRN-dependent topoisomerase removal contributes significantly to resistance against topoisomerase-trapping drugs. This study has important implications for our understanding of the role of the MRN complex and CtIP in resistance of cells to a clinically important group of anticancer drugs.

Item Type: Article
Additional Information: GDSC274
Subjects: Q Science
Depositing User: Gee Wheatley
Date Deposited: 09 Apr 2010
Last Modified: 16 Mar 2018 16:14
URI: http://sro.sussex.ac.uk/id/eprint/2282
Google Scholar:34 Citations

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