Yeast lsm pro-apoptotic mutants show defects in S-phase entry and progression

Cell Cycle. 2010 Oct 1;9(19):3991-6. doi: 10.4161/cc.9.19.13210. Epub 2010 Oct 29.

Abstract

Expression of the histone genes is tightly coupled to rates of DNA synthesis in yeast and histone mRNAs are modulated both transcriptionally and post-transcriptionally. Trf4 and Trf5, poly(A) polymerases, that mediates polyadenylation and consequent degradation) and Rrp6, an exosome component, play a role in the regulation of histone mRNA levels. In this paper we show that in the mRNA degradation mutant Kllsm4Δ1, histone mRNAs are induced early in the S-phase and maintained at high level all along the entire cell cycle due to a delay in the exit from S-phase and/or entry into M-phase. The overexpression of the HIR1 gene (Histone transcriptional repressor), previously isolated as a multicopy suppressor of the apoptotic phenotypes observed in Kllsm4Δ1, can also restore the normal cycling of histone genes expression. We also found that low doses of hydroxyurea neutralize the onset of the apoptotic phenotypes in Kllsm4Δ1, as well in another mRNA decapping mutants (lsm1) and, in addition, increase the chronological lifespan in both strains suggesting that an entry delay into the S phase can recover some cellular defects in decapping mutants.

MeSH terms

  • Apoptosis / genetics*
  • Histones / genetics
  • Hydroxyurea / pharmacology
  • Mutation
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Nucleic Acid Synthesis Inhibitors / pharmacology
  • Oxidative Stress
  • RNA Caps / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Ribonucleoprotein, U4-U6 Small Nuclear / genetics*
  • Ribonucleoprotein, U4-U6 Small Nuclear / metabolism*
  • S Phase / drug effects
  • S Phase / physiology*
  • Saccharomyces cerevisiae / cytology*
  • Saccharomyces cerevisiae / physiology*
  • Saccharomyces cerevisiae Proteins / genetics*
  • Saccharomyces cerevisiae Proteins / metabolism*

Substances

  • HIR1 protein, S cerevisiae
  • Histones
  • LSM4 protein, S cerevisiae
  • Nuclear Proteins
  • Nucleic Acid Synthesis Inhibitors
  • RNA Caps
  • RNA, Messenger
  • Repressor Proteins
  • Ribonucleoprotein, U4-U6 Small Nuclear
  • Saccharomyces cerevisiae Proteins
  • Hydroxyurea