ArticlePLoS genetics2020
Separable, Ctf4-mediated recruitment of DNA Polymerase α for initiation of DNA synthesis at replication origins and lagging-strand priming during replication elongation.
Article in PLoS genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- An updated view on lagging strand DNA replication: implications for the replication stress response.Cell cycle (Georgetown, Tex.) · 2026Article
- FACT-(H3-H4) complex stimulates Pol α activity to coordinate DNA synthesis with nucleosome assembly.Science advances · 2026Article
- Elevated dNTP Pool Levels Impair Homologous Recombination and Enhance Glioblastoma Sensitivity to Irradiation and Temozolomide.International journal of molecular sciences · 2026Article
- Increased replication-associated single-stranded DNA promotes formaldehyde-induced mutagenesis.bioRxiv : the preprint server for biology · 2026Article
- Mechanistic models of asymmetric hand-over-hand translocation and nucleosome navigation by CMG helicase.Nature communications · 2025Article
- Eukaryotic Lagging Strand Synthesis is Distributive.bioRxiv : the preprint server for biology · 2025Article
- DNA polymerase α/primase extraction from chromatin by VCP/p97 restricts ATR activation during unperturbed DNA replication.Nature communications · 2025Article
- Stabilization of expandable DNA repeats by the replication factor Mcm10 promotes cell viability.Nature communications · 2024Article
- Dominant and genome-wide formation of DNA:RNA hybrid G-quadruplexes in living yeast cells.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Review
- How Pol α-primase is targeted to replisomes to prime eukaryotic DNA replication.Molecular cell · 2023Article
- Unscheduled DNA replication in G1 causes genome instability and damage signatures indicative of replication collisions.Nature communications · 2022Article
- Yeast Stn1 promotes MCM to circumvent Rad53 control of the S phase checkpoint.Current genetics · 2022Article
- Review
- Post-replicative nick translation occurs on the lagging strand during prolonged depletion of DNA ligase I in Saccharomyces cerevisiae.G3 (Bethesda, Md.) · 2021Article
- Repriming DNA synthesis: an intrinsic restart pathway that maintains efficient genome replication.Nucleic acids research · 2021Review
- Preservation of lagging strand integrity at sites of stalled replication by Pol α-primase and 9-1-1 complex.Science advances · 2021Article
- Shaping human telomeres: from shelterin and CST complexes to telomeric chromatin organization.Nature reviews. Molecular cell biology · 2021Review
- Analysis of APOBEC-induced mutations in yeast strains with low levels of replicative DNA polymerases.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
During eukaryotic DNA replication, DNA polymerase alpha/primase (Pol α) initiates synthesis on both the leading and lagging strands. It is unknown whether leading- and lagging-strand priming are mechanistically identical, and whether Pol α associates processively or distributively with the replisome. Here, we titrate cellular levels of Pol α in S. cerevisiae and analyze Okazaki fragments to study both replication initiation and ongoing lagging-strand synthesis in vivo. We observe that both Okazaki fragment initiation and the productive firing of replication origins are sensitive to Pol α abundance, and that both processes are disrupted at similar Pol α concentrations. When the replisome adaptor protein Ctf4 is absent or cannot interact with Pol α, lagging-strand initiation is impaired at Pol α concentrations that still support normal origin firing. Additionally, we observe that activation of the checkpoint becomes essential for viability upon severe depletion of Pol α. Using strains in which the Pol α-Ctf4 interaction is disrupted, we demonstrate that this checkpoint requirement is not solely caused by reduced lagging-strand priming. Our results suggest that Pol α recruitment for replication initiation and ongoing lagging-strand priming are distinctly sensitive to the presence of Ctf4. We propose that the global changes we observe in Okazaki fragment length and origin firing efficiency are consistent with distributive association of Pol α at the replication fork, at least when Pol α is limiting.
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