ArticleThe Journal of biological chemistry2009
A DNA polymerase-{alpha}{middle dot}primase cofactor with homology to replication protein A-32 regulates DNA replication in mammalian cells.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 122 papers.
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Who cites it
122 citing papers in PubMed, 166 citations in OpenAlex.
- CST complex promotes second-strand synthesis in break-induced replication.Nature structural & molecular biology · 2026Article
- Stn1 promotes zebrafish oocyte development via amplifying Wnt/β-catenin signaling.EMBO reports · 2026Article
- Conditional deletion of human STN1 leads to telomere dysfunction, genome instability and proliferation defects.Journal of cell science · 2026Article
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- Human CST Stimulates Base Excision Repair to Prevent the Accumulation of Oxidative DNA Damage.Journal of molecular biology · 2024Article
- Article
- Cytotoxicity and Multi-Enzyme Inhibition ofPlants (Basel, Switzerland) · 2024Article
- Replication Protein A, the Main Eukaryotic Single-Stranded DNA Binding Protein, a Focal Point in Cellular DNA Metabolism.International journal of molecular sciences · 2024Review
- Telomere C-Strand Fill-In Machinery: New Insights into the Human CST-DNA Polymerase Alpha-Primase Structures and Functions.Sub-cellular biochemistry · 2024Review
- POT1 recruits and regulates CST-Polα/Primase at human telomeres.bioRxiv : the preprint server for biology · 2023Article
- Models for human telomere C-strand fill-in by CST-Polα-primase.Trends in biochemical sciences · 2023Review
- Pot1b -/- tumors activate G-quadruplex-induced DNA damage to promote telomere hyper-elongation.Nucleic acids research · 2023Article
- CST-Polα/Primase: the second telomere maintenance machine.Genes & development · 2023Review
- EPAS1 prevents telomeric damage-induced senescence by enhancing transcription ofZoological research · 2023Article
- Deficiency in mammalian STN1 promotes colon cancer development via inhibiting DNA repair.Science advances · 2023Article
- Review
- Association of Mutations in Replicative DNA Polymerase Genes with Human Disease: Possible Application ofInternational journal of molecular sciences · 2023Review
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62 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
alpha-Accessory factor (AAF) stimulates the activity of DNA polymerase-alpha.primase, the only enzyme known to initiate DNA replication in eukaryotic cells ( Goulian, M., Heard, C. J., and Grimm, S. L. (1990) J. Biol. Chem. 265, 13221-13230 ). We purified the AAF heterodimer composed of 44- and 132-kDa subunits from cultured cells and identified full-length cDNA clones using amino acid sequences from internal peptides. AAF-132 demonstrated no homologies to known proteins; AAF-44, however, is evolutionarily related to the 32-kDa subunit of replication protein A (RPA-32) and contains an oligonucleotide/oligosaccharide-binding (OB) fold domain similar to the OB fold domains of RPA involved in single-stranded DNA binding. Epitope-tagged versions of AAF-44 and -132 formed a complex in intact cells, and purified recombinant AAF-44 bound to single-stranded DNA and stimulated DNA primase activity only in the presence of AAF-132. Mutations in conserved residues within the OB fold of AAF-44 reduced DNA binding activity of the AAF-44.AAF-132 complex. Immunofluorescence staining of AAF-44 and AAF-132 in S phase-enriched HeLa cells demonstrated punctate nuclear staining, and AAF co-localized with proliferating cell nuclear antigen, a marker for replication foci containing DNA polymerase-alpha.primase and RPA. Small interfering RNA-mediated depletion of AAF-44 in tumor cell lines inhibited [methyl-(3)H]thymidine uptake into DNA but did not affect cell viability. We conclude that AAF shares structural and functional similarities with RPA-32 and regulates DNA replication, consistent with its ability to increase polymerase-alpha.primase template affinity and stimulate both DNA primase and polymerase-alpha activities in vitro.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.