ABSTRACT
Budding yeast Mph1 helicase and its orthologs drive multiple DNA transactions. Elucidating the mechanisms that regulate these motor proteins is central to understanding genome maintenance processes. Here, we show that the conserved histone fold MHF complex promotes Mph1-mediated repair of damaged replication forks but does not influence the outcome of DNA double-strand break repair. Mechanistically, scMHF relieves the inhibition imposed by the structural maintenance of chromosome protein Smc5 on Mph1 activities relevant to replication-associated repair through binding to Mph1 but not DNA. Thus, scMHF is a function-specific enhancer of Mph1 that enables flexible response to different genome repair situations.
Subject(s)
DNA-Binding Proteins/metabolism , DNA/metabolism , Histones/metabolism , Saccharomyces cerevisiae Proteins/metabolism , Saccharomyces cerevisiae/physiology , DEAD-box RNA Helicases/metabolism , DNA/genetics , DNA Repair , Genome, Fungal/genetics , Mutation , Protein Binding , Protein Folding , Protein Structure, Tertiary , Recombination, Genetic , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae Proteins/geneticsABSTRACT
Fluctuations in the ambient environment can trigger chromatin disruptions, involving replacement of nucleosomes or exchange of their histone subunits. Unlike canonical histones, which are available only during S-phase, replication-independent histone variants are present throughout the cell cycle and are adapted for chromatin repair. The H2A.Z variant mediates responses to environmental perturbations including fluctuations in temperature and seasonal variation. Phosphorylation of histone H2A.X rapidly marks double-strand DNA breaks for chromatin repair, which is mediated by both H2A and H3 histone variants. Other histones are used as weapons in conflicts between parasites and their hosts, which suggests broad involvement of histone variants in environmental responses beyond chromatin repair.