Oxidation state of the XRCC1 N-terminal domain regulates DNA polymerase β binding affinity

被引：59

作者：

Cuneo, Matthew J. ^{[1
]}

London, Robert E. ^{[1
]}

机构：

[1] Natl Inst Environm Hlth Sci, Struct Biol Lab, Res Triangle Pk, NC 27709 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2010年 / 107卷 / 15期

关键词：

disulfide switch; DNA repair; scaffolding protein; BASE EXCISION-REPAIR; PROTEIN; SCATTERING; PROGRAM; SYSTEM;

D O I：

10.1073/pnas.0914077107

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Formation of a complex between the XRCC1 N-terminal domain (NTD) and DNA polymerase beta (Pol beta) is central to base excision repair of damaged DNA. Two crystal forms of XRCC1-NTD complexed with Pol beta have been solved, revealing that the XRCC1-NTD is able to adopt a redox-dependent alternate fold, characterized by a disulfide bond, and substantial variations of secondary structure, folding topology, and electrostatic surface. Although most of these structural changes occur distal to the interface, the oxidized XRCC1-NTD forms additional interactions with Pol beta, enhancing affinity by an order of magnitude. Transient disulfide bond formation is increasingly recognized as an important molecular regulatory mechanism. The results presented here suggest a paradigm in DNA repair in which the redox state of a scaffolding protein plays an active role in organizing the repair complex.

引用

页码：6805 / 6810

页数：6

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