Conformational effects of a common codon 751 polymorphism on the C-terminal domain of the xeroderma pigmentosum D protein

Details

• Personal Author:
  Brandt-Rauf PW ; Dolan MA ; Freyer G ; Monaco R ; Pincus MR ; Rosal R
• Description:
  Aim: The xeroderma pigmentosum D (XPD) protein is a DNA helicase involved in the repair of DNA damage, including nucleotide excision repair (NER) and transcription-coupled repair (TCR). The C-terminal domain of XPD has been implicated in interactions with other components of the TFIIH complex, and it is also the site of a common genetic polymorphism in XPD at amino acid residue 751 (Lys->Gln). Some evidence suggests that this polymorphism may alter DNA repair capacity and increase cancer risk. The aim of this study was to investigate whether these effects could be attributable to conformational changes in XPD induced by the polymorphism. Materials and Methods: Molecular dynamics techniques were used to predict the structure of the wild-type and polymorphic forms of the C-terminal domain of XPD and differences in structure produced by the polymorphic substitution were determined. Results: The results indicate that, although the general configuration of both proteins is similar, the substitution produces a significant conformational change immediately N-terminal to the site of the polymorphism. Conclusion: These results provide support for the hypothesis that this polymorphism in XPD could affect DNA repair capability, and hence cancer risk, by altering the structure of the C-terminal domain. [Description provided by NIOSH]
• Subjects:
  Genetics Neoplasms Occupational Health Risk Assessment Risk Factors Safety
• Keywords:
  Author Keywords: Genetic Polymorphism Cancer Cell-function Cellular-function Exposure-levels Molecular-structure Molecular Dynamics Nucleotide Excision Repair Proteins Risk-factors Structure-function Correlation

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• ISSN:
  0974-6773
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Illinois ; Missouri ; New York ; OSHA Region 2 ; OSHA Region 5 ; OSHA Region 7
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  12
• Volume:
  8
• NIOSHTIC Number:
  nn:20042205
• Citation:
  J Carcinog 2009 Aug; 8:12
• Contact Point Address:
  Paul W Brandt-Rauf, School of Public Health, University of Illinois at Chicago, 1603 West Taylor Street, Room 1145, Chicago, IL 60612
• Federal Fiscal Year:
  2009
• NORA Priority Area:
  Manufacturing
• Performing Organization:
  University of Illinois at Chicago
• Peer Reviewed:
  True
• Start Date:
  20010701
• Source Full Name:
  Journal of Carcinogenesis
• End Date:
  20150831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:5db183100f8374cf5ab27cff66f42907314cacd04d8625ef67c3ebaeed00efe8cb6332938a721b017387403d471f2d425bffee7d5892a3233ed6139b053556b7
• Download URL:
  https://stacks.cdc.gov/view/cdc/194505/cdc_194505_DS1.pdf
• File Type:
  [PDF - 1.27 MB ]