Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

National Institute of Environmental Health Sciences

Use this QR code to view the newest version of this document
Use this QR code to view the newest version of this document

Your Environment. Your Health.

Publication Detail

Title: Conformational effects of a common codon 399 polymorphism on the BRCT1 domain of the XRCC1 protein.

Authors: Monaco, Regina; Rosal, Ramon; Dolan, Michael A; Pincus, Matthew R; Brandt-Rauf, Paul W

Published In Protein J, (2007 Dec)

Abstract: The X-ray cross-complementing-1 (XRCC1) protein functions as a scaffold that coordinates the activity of the cellular machinery involved in base excision repair (BER) of DNA damage. The BRCT1 domain of XRCC1 is responsible for interacting with several of the key components of the BER machinery, and it is also the site of a common genetic polymorphism in XRCC1 at amino acid residue 399 (Arg --> Gln). Experimental and epidemiologic evidence suggest that this polymorphism may alter BER capacity and increase cancer risk. The aim of this study was to investigate whether these effects could be attributable to conformational changes in XRCC1 induced by the polymorphism. Molecular dynamics techniques were used to predict the structure of the wild-type and polymorphic forms of the BRCT1 domain of XRCC1, and differences in structure produced by the polymorphic substitution were determined. The results indicate that, although the general configuration of both proteins is similar and there is little actual deviation at the site of the polymorphism itself, the substitution produces significant conformational changes at several other sites in the BRCT1 domain, including the loss of secondary structural features such as alpha helices that may be critical for protein-protein interactions. These results provide support for the hypothesis that this polymorphism in XRCC1 could affect DNA repair capability by altering the structure of the BRCT1 domain and thus the ability of XRCC1 to coordinate BER.

PubMed ID: 17899335 Exiting the NIEHS site

MeSH Terms: BRCA1 Protein/chemistry*; Codon/genetics*; DNA Repair*; DNA-Binding Proteins/genetics*; DNA-Binding Proteins/metabolism; Genetic Predisposition to Disease; Humans; Polymorphism, Genetic*; Protein Structure, Tertiary; X-ray Repair Cross Complementing Protein 1

Back
to Top