The SAGA histone acetyltransferase module targets SMC5/6 to specific genes

Epigenetics Chromatin. 2023 Feb 16;16(1):6. doi: 10.1186/s13072-023-00480-z.


Background: Structural Maintenance of Chromosomes (SMC) complexes are molecular machines driving chromatin organization at higher levels. In eukaryotes, three SMC complexes (cohesin, condensin and SMC5/6) play key roles in cohesion, condensation, replication, transcription and DNA repair. Their physical binding to DNA requires accessible chromatin.

Results: We performed a genetic screen in fission yeast to identify novel factors required for SMC5/6 binding to DNA. We identified 79 genes of which histone acetyltransferases (HATs) were the most represented. Genetic and phenotypic analyses suggested a particularly strong functional relationship between the SMC5/6 and SAGA complexes. Furthermore, several SMC5/6 subunits physically interacted with SAGA HAT module components Gcn5 and Ada2. As Gcn5-dependent acetylation facilitates the accessibility of chromatin to DNA-repair proteins, we first analysed the formation of DNA-damage-induced SMC5/6 foci in the Δgcn5 mutant. The SMC5/6 foci formed normally in Δgcn5, suggesting SAGA-independent SMC5/6 localization to DNA-damaged sites. Next, we used Nse4-FLAG chromatin-immunoprecipitation (ChIP-seq) analysis in unchallenged cells to assess SMC5/6 distribution. A significant portion of SMC5/6 accumulated within gene regions in wild-type cells, which was reduced in Δgcn5 and Δada2 mutants. The drop in SMC5/6 levels was also observed in gcn5-E191Q acetyltransferase-dead mutant.

Conclusion: Our data show genetic and physical interactions between SMC5/6 and SAGA complexes. The ChIP-seq analysis suggests that SAGA HAT module targets SMC5/6 to specific gene regions and facilitates their accessibility for SMC5/6 loading.

Keywords: Ada2; Chromatin accessibility; DNA repair; Gcn5; Gene regions; Genetic and protein–protein interactions; Histone H3K9ac acetylation; Nse3 KITE; SAGA histone acetyltransferase module; SMC5/6 complex targeting; rDNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetyltransferases / genetics
  • Carrier Proteins / metabolism
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cell Nucleus / metabolism
  • Chromatin / metabolism
  • Chromosomes / metabolism
  • DNA / metabolism
  • Histone Acetyltransferases / genetics
  • Histone Acetyltransferases / metabolism
  • Schizosaccharomyces pombe Proteins* / genetics
  • Schizosaccharomyces pombe Proteins* / metabolism
  • Schizosaccharomyces* / genetics
  • Schizosaccharomyces* / metabolism


  • Acetyltransferases
  • Carrier Proteins
  • Cell Cycle Proteins
  • Chromatin
  • DNA
  • Gcn5 protein, S pombe
  • Histone Acetyltransferases
  • Nse4 protein, S pombe
  • Schizosaccharomyces pombe Proteins
  • Smc5 protein, S pombe
  • smc6 protein, S pombe