Increased levels of lagging strand polymerase α in an adult stem cell lineage affect replication-coupled histone incorporation
Year: 2025
Type: article
Abstract: male germ line. Here, we report that components involved in lagging strand synthesis, DNA polymerases α and δ, have substantially reduced levels in stem cells compared to progenitor cells, and this promotes local asymmetry of parental histone incorporation at the replication fork. Compromising Polα genetically induces the local replication-coupled histone incorporation pattern in progenitor cells to resemble that in stem cells, seen by both nuclear localization patterns and chromatin fibers. This is recapitulated using a Polα inhibitor in a concentration-dependent manner. The local old versus new histone asymmetry is comparable between stem cells and progenitor cells at both S phase and M phase. Together, these results indicate that developmentally programmed expression of key DNA replication components is important to shape stem cell chromatin. Furthermore, manipulating one crucial DNA replication component can induce replication-coupled histone dynamics in nonstem cells to resemble those in stem cells.
Source: Science Advances
Authors: Brendon E. M. Davis, Jonathan Snedeker, Rajesh Ranjan, Matthew Wooten, Savannah Sáde Barton, Joshua Blundon, Xin Chen
Institutions: Johns Hopkins University, Howard Hughes Medical Institute
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,500
Awards: Cellular and Molecular Biology, Mechanism and Regulation of Replication-Coupled Asymmetric Histone Incorporation in Drosophila Male Germline Stem Cells, Investigating the mechanisms and generality of asymmetric histone inheritance in multiple stem cell systems, G7616213886, G8104157632, G863163989, Epigenetic Regulation of Germ Cell Differentiation from a Stem Cell Lineage, G98805469
OpenAlex ID: W4408029992