Interaction of checkpoint proteins Hus1/Rad1/Rad9 with DNA base excision repair enzyme MutY homolog in fission yeast, Schizosaccharomyces pombe

J Biol Chem. 2005 Jan 7;280(1):408-17. doi: 10.1074/jbc.M406800200. Epub 2004 Nov 8.

Abstract

The DNA glycosylase MutY homolog (MYH) is responsible for removing adenines misincorporated opposite DNA strands containing guanine or 7,8-dihydro-8-oxoguanine by base excision repair thereby preventing G:C to T:A mutations. MYH has been shown to interact with the proliferating cell nuclear antigen (PCNA) in both human and fission yeast Schizosaccharomyces pombe systems. Here we show that S. pombe (Sp) MYH physically interacts with all subunits of the PCNA-like checkpoint protein heterotrimer, SpRad9/SpRad1/SpHus1, in yeast extracts and when the individual subunits are expressed in bacteria. The SpHus1 and SpPCNA binding sites are located in discrete regions of SpMYH. Immunoprecipitation assays reveal that the interaction between SpHus1 and SpMYH increases dramatically after hydrogen peroxide treatment, and this increase in the SpHus1-SpMYH interaction correlates with the presence of SpHus1 phosphorylation. In contrast, the interaction between SpPCNA and SpMYH after hydrogen peroxide treatment remains nearly unchanged. SpMYH associates with SpHus1 in a complex of approximately 450 kDa, the reported native molecular mass of the SpRad9/SpRad1/SpHus1-MYC complex. A larger portion of SpMYH shifts to the 150-500-kDa regions after hydrogen peroxide treatment in comparison with untreated extracts. SpHus1 phosphorylation is substantially reduced in SpMYH Delta cells after hydrogen peroxide treatment. These data suggest that MYH may act as an adaptor to recruit checkpoint proteins to the DNA lesions.

Publication types

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

MeSH terms

  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • DNA Glycosylases / genetics
  • DNA Repair*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Endonucleases / genetics
  • Endonucleases / metabolism
  • Macromolecular Substances / metabolism
  • Phosphorylation
  • Protein Binding
  • Protein Subunits
  • Schizosaccharomyces / genetics*
  • Schizosaccharomyces / metabolism
  • Schizosaccharomyces pombe Proteins / genetics
  • Schizosaccharomyces pombe Proteins / metabolism

Substances

  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Macromolecular Substances
  • Protein Subunits
  • Schizosaccharomyces pombe Proteins
  • hus1 protein, S pombe
  • rad9 protein
  • Endonucleases
  • rad1 protein, S pombe
  • DNA Glycosylases
  • mutY adenine glycosylase