Association of XRCC1 and tyrosyl DNA phosphodiesterase (Tdp1) for the repair of topoisomerase I-mediated DNA lesions

被引：164

作者：

Plo, I

Liao, ZY

Barceló, JM

Kohlhagen, G

Caldecott, KW

Weinfeld, M

Pommier, Y

机构：

[1] NCI, Mol Pharmacol Lab, Ctr Canc Res, Bethesda, MD 20892 USA

[2] Univ Sussex, Brighton BN1 9RR, E Sussex, England

[3] Univ Alberta, Edmonton, AB T6G 1Z2, Canada

来源：

DNA REPAIR | 2003年 / 2卷 / 10期

基金：

加拿大健康研究院;

关键词：

camptothecin; topoisomerase I; XRCC1; transcription-mediated damage; replication-mediated DSB;

D O I：

10.1016/S1568-7864(03)00116-2

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

DNA topoisomerase I (Top 1) is converted into a cellular poison by camptothecin (CPT) and various endogenous and exogenous DNA lesions. In this study, we used X-ray repair complementation group 1 (XRCC1)-deficient and XRCC1-complemented EM9 cells to investigate the mechanism by which XRCC1 affects the cellular responses to Top I cleavage complexes induced by CPT. XRCC1 complementation enhanced survival to CPT-induced DNA lesions produced independently of DNA replication. CPT-induced comparable levels of Top I cleavage complexes (single-strand break (SSB) and DNA-protein cross-links (DPC) in both XRCC1-deficient and XRCC1-complemented cells. However, XRCC1-complemented cells repaired Top 1-induced DNA breaks faster than XRCC1-deficient cells, and exhibited enhanced tyrosyl DNA phosphodiesterase (Tdp1) and polynucleotide kinase phosphatase (PNKP) activities. XRCC1 immunoprecipitates contained Tdp1 polypeptide, and both Tdp1 and PNKP activities, indicating a functional connection between the XRCC1 single-strand break repair pathway and the repair of Top 1 covalent complexes by Tdp1 and PNKP. (C) 2003 Elsevier B.V. All rights reserved.

引用

页码：1087 / 1100

页数：14

共 78 条

[1] The CHO XRCC1 mutant, EM9, deficient in DNA ligase III activity, exhibits hypersensitivity to camptothecin independent of DNA replication [J].