Oxidation State of the XRCC1 N-terminal Domain Regulates DNA Polymerase Beta Binding Affinity
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.
- Research Organization:
- Brookhaven National Lab. (BNL), Upton, NY (United States). National Synchrotron Light Source
- Sponsoring Organization:
- DOE - OFFICE OF SCIENCE
- DOE Contract Number:
- DE-AC02-98CH10886
- OSTI ID:
- 1019606
- Report Number(s):
- BNL-95451-2011-JA; PNASA6; TRN: US201115%%247
- Journal Information:
- Proceedings of the National Academy of Sciences of the United States of America, Vol. 107, Issue 15; ISSN 0027-8424
- Country of Publication:
- United States
- Language:
- English
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