Abstract
The re-assembly of chromatin following DNA replication is a critical event in the maintenance of genome integrity. Histone H3 acetylation at K56 and phosphorylation at T45 are two important chromatin modifications that accompany chromatin assembly. Here we have identified the protein kinase Pkc1 as a key regulator that coordinates the deposition of these modifications in S. cerevisiae under conditions of replicative stress. Pkc1 phosphorylates the histone acetyl transferase Rtt109 and promotes its ability to acetylate H3K56. Our data also reveal novel cross-talk between two different histone modifications as Pkc1 also enhances H3T45 phosphorylation and this modification is required for H3K56 acetylation. Our data therefore uncover an important role for Pkc1 in coordinating the deposition of two different histone modifications that are important for chromatin assembly.
Highlights
During the cell cycle one of the key processes following DNA replication is the re-assembly of chromatin on the newly replicated DNA
When we considered the biological processes that were affected, there was a strong overlap in gene ontology (GO) terms, with over-representation of GO terms associated with processes such as ’cell wall’ and ’nucleolus’ strongly associated with both mutant strains and reciprocal effects seen with ’telomere maintenance’ and ’DNA helicase activity’ (Figure 5C and D)
Synthesised DNA must be efficiently packaged into chromatin to ensure that genome stability is maintained. This must be achieved during both an unperturbed cell cycle and under conditions of replicative stress where the cell cycle must pause to ensure DNA repair occurs before recommencing the cycle
Summary
This involves the re-deposition of both pre-existing and newly synthesised histones into intact nucleosomes (reviewed in Groth et al, 2007; Ransom et al, 2010; Gurard-Levin et al, 2014). This process must be tightly controlled and in S. cerevisiae one key event is the Rtt109-mediated modification of histone H3 by acetylation of lysine 56 (H3K56) (Han et al, 2007; Driscoll et al, 2007). In the context of an unperturbed cell cycle, Cdc7-Dbf has been shown to be a major kinase involved in controlling H3T45 phosphorylation levels (Baker et al, 2010)
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