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

Molecular Genetics and Genomics : MGG
Carmela IreneCarol S Newlon

Abstract

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 replication origins from S. cerevisiae chromosome III to create chromosomes with long interorigin gaps and identified mutations that destabilize them [originless fragment maintenance (Ofm) mutations]. ofm6-1 is an allele of HST3, a sirtuin that deacetylates histone H3K56Ac. Hst3p and Hst4p are closely related, but hst4Δ does not cause an Ofm phenotype. Expressing HST4 under the control of the HST3 promoter suppressed the Ofm phenotype of hst3Δ, indicating Hst4p, when expressed at the appropriate levels and/or at the correct time, can fully substitute for Hst3p in maintenance of ORIΔ chromosomes. H3K56Ac is the Hst3p substrate critical for chromosome maintenance. H3K56Ac-containing nucleosomes are preferentially assembled into chromatin behind replication forks. Deletion of the H3K56 acetylase and downstream chromatin assembly factors suppressed the Ofm phenotype of hst3, indicating that persistence of H3K56Ac-containing chromatin is deleterious for the maintenance of ORIΔ chromosomes, and experiments with synchronous cultures showed that it is...Continue Reading

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Citations

Sep 16, 2017·PLoS Genetics·Devika SalimJennifer L Gerton
Jun 5, 2021·DNA Repair·Ian Hammond-MartelHugo Wurtele

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Methods Mentioned

BETA
acetylation
sumoylation
ubiquitination
PCR
FACS
Flow Cytometry
SGA
two-hybrid
histone acetylation

Software Mentioned

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