AI Article Synopsis
- Histone recycling from parental DNA to new strands is crucial for passing down epigenetic information during chromatin replication.
- An experiment showed that disrupting the interaction between Mcm2 and a histone complex affects recycling, but more details about the specific mechanisms involved are still unknown.
- Simulations of yeast DNA replication revealed that histones can be recycled through different pathways and that the binding of RPA influences how much is recycled to each strand, while DNA bending by Pol ε affects where the histones end up.
Article 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11531469 | PMC |
| http://dx.doi.org/10.1038/s41467-024-53187-4 | DOI Listing |
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