ArticleNucleic acids research2014
Human PrimPol mutation associated with high myopia has a DNA replication defect.
Article in Nucleic acids research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 43 citations in OpenAlex.
- Whole-Exome Sequencing of 21 Families: Candidate Genes for Early-Onset High Myopia.International journal of molecular sciences · 2023Article
- Implications of Translesion DNA Synthesis Polymerases on Genomic Stability and Human Health.Molecular and cellular biology · 2023Article
- Leveraging the replication stress response to optimize cancer therapy.Nature reviews. Cancer · 2023Review
- Temporally distinct post-replicative repair mechanisms fill PRIMPOL-dependent ssDNA gaps in human cells.Molecular cell · 2021Article
- Refractive correction regulated gradient AC/A ratio with low-to-moderate myopia in children and adolescents.International ophthalmology · 2021Article
- To skip or not to skip: choosing repriming to tolerate DNA damage.Molecular cell · 2021Review
- PRIMPOL ready, set, reprime!Critical reviews in biochemistry and molecular biology · 2021Review
- Mechanisms for Maintaining Eukaryotic Replisome Progression in the Presence of DNA Damage.Frontiers in molecular biosciences · 2021Review
- Mechanisms of direct replication restart at stressed replisomes.DNA repair · 2020Review
- Identifying the role of PrimPol in TDF-induced toxicity and implications of its loss of function mutation in an HIV+ patient.Scientific reports · 2020Article
- Concurrent pathogenic variants in SLC6A1/NOTCH1/PRIMPOL genes in a Chinese patient with myoclonic-atonic epilepsy, mild aortic valve stenosis and high myopia.BMC medical genetics · 2020Article
- PRIMPOL-Mediated Adaptive Response Suppresses Replication Fork Reversal in BRCA-Deficient Cells.Molecular cell · 2020Article
- DNA damage tolerance in stem cells, ageing, mutagenesis, disease and cancer therapy.Nucleic acids research · 2019Review
- Engineering human PrimPol into an efficient RNA-dependent-DNA primase/polymerase.Nucleic acids research · 2017Article
- DNA Damage Tolerance by Eukaryotic DNA Polymerase and Primase PrimPol.International journal of molecular sciences · 2017Review
- Mitochondrial DNA replication: a PrimPol perspective.Biochemical Society transactions · 2017Review
- PrimPol-Prime Time to Reprime.Genes · 2017Review
- Optimization of the expression, purification and polymerase activity reaction conditions of recombinant human PrimPol.PloS one · 2017Article
- Off-Target Effects of Drugs that Disrupt Human Mitochondrial DNA Maintenance.Frontiers in molecular biosciences · 2017Review
- DNA polymerases in the mitochondria: A critical review of the evidence.Frontiers in bioscience (Landmark edition) · 2017Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
PrimPol is a primase-polymerase found in humans, and other eukaryotes, involved in bypassing lesions encountered during DNA replication. PrimPol employs both translesion synthesis and repriming mechanisms to facilitate lesion bypass by the replisome. PrimPol has been reported to be a potential susceptibility gene associated with the development of myopia. Mutation of tyrosine 89 to aspartic acid (PrimPolY89D) has been identified in a number of cases of high myopia, implicating it in the aetiology of this disorder. Here, we examined whether this mutation resulted in any changes in the molecular and cellular activities associated with human PrimPol. We show that PrimPolY89D has a striking decrease in primase and polymerase activities. The hydrophobic ring of tyrosine is important for retaining wild-type extension activity. We also demonstrate that the decreased activity of PrimPolY89D is associated with reduced affinities for DNA and nucleotides, resulting in diminished catalytic efficiency. Although the structure and stability of PrimPolY89D is altered, its fidelity remains unchanged. This mutation also reduces cell viability after DNA damage and significantly slows replication fork rates in vivo. Together, these findings establish that the major DNA replication defect associated with this PrimPol mutant is likely to contribute to the onset of high myopia.
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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.