Hst3p, a histone deacetylase, promotes maintenance of Saccharomyces cerevisiae chromosome III lacking efficient replication origins

• DOI: 10.1007/s00438-015-1105-8
• Publication Date: 2015-08-28T14:43:20Z
• Authors: Carmela Irene; James F. Theis; David Gresham; Patricia Soteropo...; Carol S. Newlon
• Keywords: Histone code; Replication timing

Long gaps between active replication origins probably occur frequently during chromosome replication, but little is known about how cells cope with them. To address this issue, we deleted from S. cerevisiae III to create chromosomes long interorigin and identified mutations that destabilize them [originless fragment maintenance (Ofm) mutations]. ofm6-1 an allele of HST3, a sirtuin deacetylates histone H3K56Ac. Hst3p Hst4p are closely related, hst4Δ does not cause Ofm phenotype. Expressing HST4 under the control HST3 promoter suppressed phenotype hst3Δ, indicating Hst4p, when expressed at appropriate levels and/or correct time, can fully substitute for in ORIΔ chromosomes. H3K56Ac substrate critical maintenance. H3K56Ac-containing nucleosomes preferentially assembled into chromatin behind forks. Deletion H3K56 acetylase downstream assembly factors hst3, persistence deleterious chromosomes, experiments synchronous cultures showed it causes loss. This work shows while normal tolerate hyperacetylation H3K56Ac, deacetylation by required stable gap. The first report instability hst3 single mutant.