Replication stress inhibits synthesis of histone mRNAs in yeast by removing Spt10p and Spt21p from the histone promoters

Abstract

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Decoupling of transcript and protein concentrations ensures budding yeast histone homeostasis in different nutrient conditions

“…2B). Consistent with previous studies ( 36, 37 ), we found that histone mRNAs in YPD have short half-lives, whereas ACT1 mRNA is more stable. Moreover, we showed that both histone and ACT1 mRNAs are significantly more stable in poor compared to rich nutrient conditions.…”

“…Relative changes in mRNA concentrations were measured by RT-qPCR as described above. Target-specific primers were designed to bind to the HTB1, HTB2 and ACT1 coding sequences, respectively ( 36 ). The half-lives of histone and ACT1 mRNAs were calculated by fitting a single exponential function to the obtained mRNA decay curves.…”

Gene loss and cis-regulatory novelty shaped core histone gene evolution in the apiculate yeastHanseniaspora uvarum

“…In S . cerevisiae, histone synthesis is inhibited following a DNA replication block with the treatment of hydroxyurea (HU) via a specific regulatory coupling (Bhagwat et al . 2021), which is likely mediated by the HIR complex ( hi stone regulatory genes ( HIR1 , HIR2 , HIR3 ) and h istone p eriodic c ontrol gene ( HPC2 )).…”

“…In most eukaryotes, histone protein synthesis is tightly coupled to the status of DNA replication (Eriksson et al 2012;Rattray and Müller 2012;Kurat et al 2014). In S. cerevisiae, histone synthesis is inhibited following a DNA replication block with the treatment of hydroxyurea (HU) via a specific regulatory coupling (Bhagwat et al 2021), which is likely mediated by the HIR complex (histone regulatory genes (HIR1, HIR2, HIR3) and histone periodic control gene (HPC2)). Given the altered cell cycle dynamics, we were curious whether histone synthesis was dependent on DNA synthesis in H. uvarum.…”

“…Tight control of the regulation of core histones throughout the cell cycle ensures the proper function of DNAtemplated processes (Eriksson et al 2012). Proper stoichiometry between nucleosomes and total DNA content is partly controlled through replication-coupled synthesis of histones (Robbins and Borun 1967), evidenced by experimental inhibition of DNA synthesis leading to rapid repression of histone synthesis (Osley 1991;Rattray and Müller 2012;Bhagwat et al 2021) Moreover, misexpression of histones outside of S-phase characteristically leads to cellular toxicity and growth arrest (Kurat et al 2014).…”