Centrin 2 stimulates nucleotide excision repair by interacting with xeroderma pigmentosum group C protein

Mol Cell Biol. 2005 Jul;25(13):5664-74. doi: 10.1128/MCB.25.13.5664-5674.2005.


Xeroderma pigmentosum group C (XPC) protein plays a key role in DNA damage recognition in global genome nucleotide excision repair (NER). The protein forms in vivo a heterotrimeric complex involving one of the two human homologs of Saccharomyces cerevisiae Rad23p and centrin 2, a centrosomal protein. Because centrin 2 is dispensable for the cell-free NER reaction, its role in NER has been unclear. Binding experiments with a series of truncated XPC proteins allowed the centrin 2 binding domain to be mapped to a presumed alpha-helical region near the C terminus, and three amino acid substitutions in this domain abrogated interaction with centrin 2. Human cell lines stably expressing the mutant XPC protein exhibited a significant reduction in global genome NER activity. Furthermore, centrin 2 enhanced the cell-free NER dual incision and damaged DNA binding activities of XPC, which likely require physical interaction between XPC and centrin 2. These results reveal a novel vital function for centrin 2 in NER, the potentiation of damage recognition by XPC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Calcium-Binding Proteins
  • Cell Cycle Proteins / chemistry
  • Cell Cycle Proteins / metabolism*
  • Cell Line
  • Conserved Sequence
  • DNA / genetics
  • DNA / metabolism
  • DNA Damage / radiation effects
  • DNA Repair*
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism*
  • Humans
  • Molecular Sequence Data
  • Mutation
  • Protein Binding
  • Protein Structure, Tertiary
  • Sequence Homology, Amino Acid
  • Ultraviolet Rays
  • Xeroderma Pigmentosum / genetics
  • Xeroderma Pigmentosum / metabolism


  • CETN2 protein, human
  • Calcium-Binding Proteins
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • XPC protein, human
  • DNA