Wdr70 regulates histone modification and genomic maintenance in fission yeast

Biochim Biophys Acta Mol Cell Res. 2020 May;1867(5):118665. doi: 10.1016/j.bbamcr.2020.118665. Epub 2020 Jan 30.

Abstract

Eukaryotic genomes are packaged into highly condensed chromatin and this repressive chromatin barrier can be overcome by altering the chromatin structure via histone modification enzymes. Here, we report Wdr70 in Schizosaccharomyces pombe (spWdr70) plays important roles in multiple cellular processes including cell cycle progression, chromatin structure and DNA repair. Depletion of Wdr70 gene causes cell cycle delay, hypersensitivity to DNA damage reagents and quick phenotypic changes. Moreover, we observed strong genetic interaction between Wdr70 and genes regulating checkpoint and homologous recombination (HR), pinpointing the function of Wdr70 to DNA end resection. Finally, we show that the function of Wdr70 could be attributed to monoubiquitination of histone H2B (uH2B) in the vicinity of DNA double strand breaks (DSBs). Taken together, our data reveal that Wdr70 and H2B monoubiquitination-dependent chromatin modulation is required for chromatin homeostasis and genetic stability.

Keywords: Cell cycle; DNA end resection; Histone modification; Homologous recombination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Gene Deletion
  • Genome, Fungal
  • Genomic Instability*
  • Histone Code
  • Histones / metabolism*
  • Schizosaccharomyces / genetics*
  • Schizosaccharomyces / metabolism
  • Schizosaccharomyces pombe Proteins / chemistry
  • Schizosaccharomyces pombe Proteins / genetics
  • Schizosaccharomyces pombe Proteins / metabolism*
  • Ubiquitination
  • WD40 Repeats

Substances

  • Histones
  • Schizosaccharomyces pombe Proteins