DistinctrRequirements 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) DistinctrRequirements 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 Rad32(Mre11) nuclease activity is involved in the removal of both Top2 from 5' DNA ends as well as Top1 from 3' ends in vivo. A ctp1(ctIP) deletion is defective for Top2 removal but overproficient for Top1 removal, suggesting that Ctp1(ctIP) 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
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
Depositing User: Edgar Hartsuiker
Date Deposited: 06 Feb 2012 19:33
Last Modified: 10 Jul 2013 10:04
URI: http://sro.sussex.ac.uk/id/eprint/21292
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