Elucidate the Molecular Mechanisms by which DNA Replication is Coupled to Nucleosome Assembly During DNA Replication in Budding Yeast
Regulation of replication coupled nucleosome assembly pathway in yeast.
There are two tightly regulated pathways for assembling replicating DNA into nucleosomes immediately following DNA replication. First is the transfer of parental histones behind replication forks following DNA replication. Second, newly synthesized histones are deposited onto replicating DNA with the help of histone H3-H4 chaperones such as CAF-1, Asf1 and Rtt106. Using budding yeast, we are studying two aspects of the regulation of these processes. First, we are determining how histone acetyltransferases including Rtt109 and Gcn5 regulate assembly of newly-synthesized H3-H4 onto replicating DNA. Second, we are addressing how posttranslational modifications on parental histones are propagated into daughter cells during mitotic cell division. Together, these studies will address the fundamental mechanisms by which nucleosomes are formed immediately following DNA replication and shed light on how genome instability will occur through deregulation of these processes.