1. Molecular mechanism of parental H3/H4 recycling at a replication fork.
- Author
-
Nagae F, Murayama Y, and Terakawa T
- Subjects
- Cell Cycle Proteins metabolism, Cell Cycle Proteins genetics, DNA Polymerase II metabolism, DNA Polymerase II genetics, Replication Protein A metabolism, DNA, Fungal metabolism, DNA, Fungal genetics, Protein Binding, Chromatin metabolism, Chromatin genetics, Histones metabolism, Histones genetics, DNA Replication, Saccharomyces cerevisiae Proteins metabolism, Saccharomyces cerevisiae Proteins genetics, Saccharomyces cerevisiae metabolism, Saccharomyces cerevisiae genetics, Molecular Dynamics Simulation
- Abstract
In chromatin replication, faithful recycling of histones from parental DNA to replicated strands is essential for maintaining epigenetic information across generations. A previous experiment has revealed that disrupting interactions between the N-terminal tail of Mcm2, a subunit in DNA replication machinery, and a histone H3/H4 tetramer perturb the recycling. However, the molecular pathways and the factors that regulate the ratio recycled to each strand and the destination location are yet to be revealed. Here, we performed molecular dynamics simulations of yeast DNA replication machinery, an H3/H4 tetramer, and replicated DNA strands. The simulations demonstrated that histones are recycled via Cdc45-mediated and unmediated pathways without histone chaperones, as our in vitro biochemical assays supported. Also, RPA binding regulated the ratio recycled to each strand, whereas DNA bending by Pol ε modulated the destination location. Together, the simulations provided testable hypotheses, which are vital for elucidating the molecular mechanisms of histone recycling., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF