Molecular mechanisms of histone inheritance during DNA replication

In eukaryotic cells, DNA is packaged into chromatin and partitioned into distinct functional regions. Nucleosomes within these regions contain specific types of histones and post-translational modifications (PTMs) that modulate chromatin structure and dynamics. During DNA replication, parental nucleosomes are disassembled ahead of the replication fork, followed by their restoration on daughter strands from recycled parental and new histones. Local histone recycling during replication is central to chromatin maintenance but the molecular mechanisms underlying this process are poorly understood. I have developed a real-time, single-molecule imaging platform that tracks nucleosome dynamics during DNA replication at an unprecedented spatiotemporal resolution. I will use this novel technology, and combine it with biochemical and biophysical methods, to uncover how histone variants and PTMs affect nucleosome dynamics during replication. These studies will provide mechanistic insight into replication-coupled histone inheritance and shed light on how chromatin structures are maintained.