The process of coordinated DNA replication and
nucleosome assembly, termed replication-coupled (RC)
nucleosome assembly, is important for the maintenance of genome integrity. Loss of genome integrity is linked to aging and
cancer. RC
nucleosome assembly involves deposition of
histone H3-H4 by the
histone chaperones CAF-1, Rtt106 and Asf1 onto newly-replicated
DNA. Coordinated actions of these three
histone chaperones are regulated by modifications on the
histone proteins. One such modification is
histone H3 lysine 56 acetylation (H3K56Ac), a mark of newly-synthesized
histone H3 that regulates the interaction between H3-H4 and the
histone chaperones CAF-1 and Rtt106 following DNA replication and DNA repair. Recently, we have shown that the
lysine acetyltransferase Gcn5 and H3 N-terminal tail
lysine acetylation also regulates the interaction between H3-H4 and CAF-1 to promote the deposition of newly-synthesized
histones. Genetic studies indicate that Gcn5 and Rtt109, the H3K56Ac
lysine acetyltransferase, function in parallel to maintain
genome stability. Utilizing synthetic genetic array analysis, we set out to identify additional genes that function in parallel with Gcn5 in response to DNA damage. We summarize here the role of Gcn5 in
nucleosome assembly and suggest that Gcn5 impacts genome integrity via multiple mechanisms, including
nucleosome assembly.