Rtt109 effect on replication speed via histone acetylation
The wrapping of DNA around histone octamers challenges processes that use DNA as their template. In-vitro, DNA replication through chromatin depends on histone modifiers, raising the possibility that cells modify histones to optimize replication fork progression in-vivo. We previously reported that a wave of H3K9 acetylation progresses ~3-5 kb ahead of the replication fork in budding yeast, but whether this wave contributes to replication dynamics remained unknown. Here, we show that the replication fork velocity increases when deleting Rtt109, the enzyme required for the pre-replication acetylation wave. Rtt109 acetylates histone H3 on H3K56 and on N-terminal residues prior to DNA incorporation. Using histone mutants, we find that Rtt109-dependent N-terminal acetylation regulates fork velocity, while H3K56 acetylation contributes to replication dynamics only when N-terminal acetylation is compromised. We propose that acetylation of newly synthesized histones slows replication by promoting replacement of nucleosomes evicted by the incoming fork, thereby protecting genome integrity.