ArticlePloS one2009
DNA polymerase delta is required for early mammalian embryogenesis.
Article in PloS one, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 45 citations in OpenAlex.
- Combined immunodeficiency caused by a loss-of-function mutation in DNA polymerase delta 1.The Journal of allergy and clinical immunology · 2020Trial
- Rare germline variants in POLE and POLD1 encoding the catalytic subunits of DNA polymerases ε and δ in glioma families.Acta neuropathologica communications · 2023Article
- DNA polymerase delta interacting protein 3 facilitates the activation and maintenance of DNA damage checkpoint in response to replication stress.Animal models and experimental medicine · 2022Article
- A hypomorphic mutation in Pold1 disrupts the coordination of embryo size expansion and morphogenesis during gastrulation.Biology open · 2022Article
- Review
- The POLD1Scientific reports · 2020Article
- ShRNA-based POLD2 expression knockdown sensitizes glioblastoma to DNA-Damaging therapeutics.Cancer letters · 2020Article
- POLD1 variants leading to reduced polymerase activity can cause hearing loss without syndromic features.Human mutation · 2020Article
- Inactivating Mutations in Exonuclease and Polymerase Domains in DNA Polymerase Delta Alter Sensitivities to Inhibitors of dNTP Synthesis.DNA and cell biology · 2020Article
- A Survey of Essential Genome Stability Genes Reveals That Replication Stress Mitigation Is Critical for Peri-Implantation Embryogenesis.Frontiers in cell and developmental biology · 2020Review
- Polμ tumor variants decrease the efficiency and accuracy of NHEJ.Nucleic acids research · 2017Article
- The dominant role of proofreading exonuclease activity of replicative polymerase ε in cellular tolerance to cytarabine (Ara-C).Oncotarget · 2017Article
- Review
- miR-155 Overexpression Promotes Genomic Instability by Reducing High-fidelity Polymerase Delta Expression and Activating Error-Prone DSB Repair.Molecular cancer research : MCR · 2016Article
- A synthetic lethal screen identifies ATR-inhibition as a novel therapeutic approach for POLD1-deficient cancers.Oncotarget · 2016Article
- Germline mutation rates and the long-term phenotypic effects of mutation accumulation in wild-type laboratory mice and mutator mice.Genome research · 2015Article
- The POLD3 subunit of DNA polymerase δ can promote translesion synthesis independently of DNA polymerase ζ.Nucleic acids research · 2015Article
- Loss of Pol32 in Drosophila melanogaster causes chromosome instability and suppresses variegation.PloS one · 2015Article
- The disparity mutagenesis model predicts rescue of living things from catastrophic errors.Frontiers in genetics · 2014Review
- The CHR site: definition and genome-wide identification of a cell cycle transcriptional element.Nucleic acids research · 2014Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIn eukaryotic cells, DNA polymerase delta (Poldelta), whose catalytic subunit p125 is encoded in the Pold1 gene, plays a central role in chromosomal DNA replication, repair, and recombination. However, the physiological role of the Poldelta in mammalian development has not been thoroughly investigated. METHODOLOGY/PRINCIPAL
findingsTo examine this role, we used a gene targeting strategy to generate two kinds of Pold1 mutant mice: Poldelta-null (Pold1(-/-)) mice and D400A exchanged Poldelta (Pold1(exo/exo)) mice. The D400A exchange caused deficient 3'-5' exonuclease activity in the Poldelta protein. In Poldelta-null mice, heterozygous mice developed normally despite a reduction in Pold1 protein quantity. In contrast, homozygous Pold1(-/-) mice suffered from peri-implantation lethality. Although Pold1(-/-) blastocysts appeared normal, their in vitro culture showed defects in outgrowth proliferation and DNA synthesis and frequent spontaneous apoptosis, indicating Poldelta participates in DNA replication during mouse embryogenesis. In Pold1(exo/exo) mice, although heterozygous Pold1(exo/+) mice were normal and healthy, Pold1(exo/exo) and Pold1(exo/-) mice suffered from tumorigenesis.
conclusionsThese results clearly demonstrate that DNA polymerase delta is essential for mammalian early embryogenesis and that the 3'-5' exonuclease activity of DNA polymerase delta is dispensable for normal development but necessary to suppress tumorigenesis.
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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.