Partitioning of Parental Histones Between Leading and Lagging Strands is Modulated by DNA Polymerase Dosage

The N-terminal region of Pol1, the catalytic subunit of DNA polymerase α, has previously been implicated in chaperoning parental histone recycling. In this study, we identify a single amino acid mutation in the C-terminal region of Saccharomyces cerevisiae Pol1 (pol1-F1396S) that destabilizes the protein and disrupts the transfer of parental histones to the lagging strand during DNA replication.

As a primary consequence, pol1-F1396S cells exhibit decreased chromatin stability. Furthermore, we demonstrate that the cellular abundance—or dosage—of all three DNA polymerases (Pol α, Pol δ, and Pol ε) influences the distribution of parental histones between the leading and lagging strands, revealing a dosage-sensitive mechanism of epigenetic regulation during DNA replication.