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

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 Kllsm4?1, histone mRNAs are induced early in S phase and maintained at high levels all along the entire cell cycle due to a delay in 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 Kllsm4?1, can also restore the normal cycling of histone gene expression. We also found that low doses of hydroxyurea neutralize the onset of the apoptotic phenotypes in Kllsm4?1, as well in another mRNA decapping mutant (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.