Physical and functional interactions between MutY glycosylase homologue (MYH) and checkpoint proteins Rad9-Rad1-Hus1

Biochem J. 2006 Nov 15;400(1):53-62. doi: 10.1042/BJ20060774.


The MYH (MutY glycosylase homologue) increases replication fidelity by removing adenines or 2-hydroxyadenine misincorporated opposite GO (7,8-dihydro-8-oxo-guanine). The 9-1-1 complex (Rad9, Rad1 and Hus1 heterotrimer complex) has been suggested as a DNA damage sensor. Here, we report that hMYH (human MYH) interacts with hHus1 (human Hus1) and hRad1 (human Rad1), but not with hRad9. In addition, interactions between MYH and the 9-1-1 complex, from both the fission yeast Schizosaccharomyces pombe and human cells, are partially interchangeable. The major Hus1-binding site is localized to residues 295-350 of hMYH and to residues 245-293 of SpMYH (S. pombe MYH). Val315 of hMYH and Ile261 of SpMYH play important roles for their interactions with Hus1. hHus1 protein and the 9-1-1 complex of S. pombe can enhance the glycosylase activity of SpMYH. Moreover, the interaction of hMYH-hHus1 is enhanced following ionizing radiation. A significant fraction of the hMYH nuclear foci co-localizes with hRad9 foci in H2O2-treated cells. These results reveal that the 9-1-1 complex plays a direct role in base excision repair.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus / drug effects
  • Amino Acid Sequence
  • Binding Sites / genetics
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Nucleus / metabolism
  • DNA Glycosylases / genetics
  • DNA Glycosylases / metabolism*
  • Exonucleases / genetics
  • Exonucleases / metabolism*
  • Glutathione Transferase / genetics
  • Glutathione Transferase / metabolism
  • HeLa Cells
  • Humans
  • Hydrogen Peroxide / pharmacology
  • Molecular Sequence Data
  • Protein Binding
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Schizosaccharomyces / genetics
  • Schizosaccharomyces / metabolism
  • Schizosaccharomyces pombe Proteins / genetics
  • Schizosaccharomyces pombe Proteins / metabolism
  • Sequence Homology, Amino Acid


  • Cell Cycle Proteins
  • HUS1 protein, human
  • HUS1B protein, human
  • Recombinant Fusion Proteins
  • Schizosaccharomyces pombe Proteins
  • rad9 protein
  • Hydrogen Peroxide
  • Glutathione Transferase
  • Exonucleases
  • Rad1 protein, human
  • DNA Glycosylases
  • mutY adenine glycosylase