During cell division, chromatin assembly is tightly coupled with DNA replication to ensure correct propagation of epigenetic information and maintain genome stability. This process is termed DNA replication-coupled (RC) nucleosome assembly/disassembly. Dysregulation of DNA RC nucleosome assembly/disassembly has been implicated in cancer and other diseases. Histone chaperones are a group of proteins that play an integral part in DNA RC nucleosome assembly by binding histones and facilitating nucleosome formation. My research aims to understand how nucleosome assembly/disassembly is regulated during S phase of the cell cycle, a key step in the inheritance of epigenetic information. Here, I show that in Saccharomycescerevisiae, acetylation of H3 at lysine 56 (H3K56Ac) regulates RC nucleosome assembly by promoting the interaction of histones H3-H4 with two histone chaperones, CAF-1 and Rtt106. Moreover, Rtt106 specifically “reads” H3K56Ac through a novel acetyl-lysine binding module, which is different from the bromodomain, a wellknown acetyl-lysine recognition motif. Finally, I discuss a novel function of FACT, another protein complex that binds H3K56Ac, in the maintenance of nucleosome stability and how FACT links nucleosome assembly/disassembly to DNA replication. Based on these findings, I propose a model in which different histone chaperones coordinate with each other and regulate RC nucleosome assembly/disassembly, thus maintaining genome stability and ensuring the propagation of epigenetic states.

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