Phosphorylation states of cell cycle and DNA repair proteins can be altered by the nsSNPs

BMC Cancer. 2005 Aug 19:5:107. doi: 10.1186/1471-2407-5-107.

Abstract

Background: Phosphorylation is a reversible post-translational modification that affects the intrinsic properties of proteins, such as structure and function. Non-synonymous single nucleotide polymorphisms (nsSNPs) result in the substitution of the encoded amino acids and thus are likely to alter the phosphorylation motifs in the proteins.

Methods: In this study, we used the web-based NetPhos tool to predict candidate nsSNPs that either introduce or remove putative phosphorylation sites in proteins that act in DNA repair and cell cycle pathways.

Results: Our results demonstrated that a total of 15 nsSNPs (16.9%) were likely to alter the putative phosphorylation patterns of 14 proteins. Three of these SNPs (CDKN1A-S31R, OGG1-S326C, and XRCC3-T241M) have already found to be associated with altered cancer risk. We believe that this set of nsSNPs constitutes an excellent resource for further molecular and genetic analyses.

Conclusion: The novel systematic approach used in this study will accelerate the understanding of how naturally occurring human SNPs may alter protein function through the modification of phosphorylation mechanisms and contribute to disease susceptibility.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Amino Acid Motifs
  • Amino Acid Sequence
  • Cell Cycle
  • Computational Biology
  • DNA Repair*
  • Gene Expression Regulation, Neoplastic*
  • Genetic Predisposition to Disease*
  • Humans
  • Models, Genetic
  • Molecular Sequence Data
  • Phosphorylation
  • Polymorphism, Single Nucleotide*