Distinct Requirements for the Rad32Mre11 Nuclease and Ctp1CtIP in the Removal of Covalently Bound Topoisomerase I and II from DNA

被引：154

作者：

Hartsuiker, Edgar ^{[1
]}

Neale, Matthew J. ^{[1
]}

Carr, Antony M. ^{[1
]}

机构：

[1] Univ Sussex, Genome Damage & Stabil Ctr, Brighton BN1 9RQ, E Sussex, England

来源：

MOLECULAR CELL | 2009年 / 33卷 / 01期

关键词：

STRAND BREAK REPAIR; SACCHAROMYCES-CEREVISIAE; SCHIZOSACCHAROMYCES-POMBE; SPINOCEREBELLAR ATAXIA; PHOSPHODIESTERASE TDP1; COMPLEX; RECOMBINATION; PROTEIN; MRE11; GENE;

D O I：

10.1016/j.molcel.2008.11.021

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：117 / 123

页数：7

共 36 条

[1] Molecular characterization of the role of the Schizosaccharomyces pombe nip1+/ctp1+ gene in DNA double-strand break repair in association with the Mre11-Rad50-Nbs1 coraplex [J].