Interaction of replication factor Sld3 and histone acetyl transferase Esa1 alleviates gene silencing and promotes the activation of late and dormant replication origins

Genetics. 2021 Mar 3;217(1):1-11. doi: 10.1093/genetics/iyaa001.

Abstract

DNA replication in eukaryotes is a multi-step process that consists of three main reactions: helicase loading (licensing), helicase activation (firing), and nascent DNA synthesis (elongation). Although the contributions of some chromatin regulatory factors in the licensing and elongation reaction have been determined, their functions in the firing reaction remain elusive. In the budding yeast Saccharomyces cerevisiae, Sld3, Sld7, and Cdc45 (3-7-45) are rate-limiting in the firing reaction and simultaneous overexpression of 3-7-45 causes untimely activation of late and dormant replication origins. Here, we found that 3-7-45 overexpression not only activated dormant origins in the silenced locus, HMLα, but also exerted an anti-silencing effect at this locus. For these, interaction between Sld3 and Esa1, a conserved histone acetyltransferase, was responsible. Moreover, the Sld3-Esa1 interaction was required for the untimely activation of late origins. These results reveal the Sld3-Esa1 interaction as a novel level of regulation in the firing reaction.

Keywords: DNA replication; Esa1; Sld3; origin firing; silencing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Regulation, Fungal*
  • Gene Silencing*
  • Histone Acetyltransferases / genetics
  • Histone Acetyltransferases / metabolism*
  • Replication Origin
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*

Substances

  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Saccharomyces cerevisiae Proteins
  • Sld3 protein, S cerevisiae
  • Esa1 protein, S cerevisiae
  • Histone Acetyltransferases