ArticleThe EMBO journal2015
Polynucleotide kinase-phosphatase enables neurogenesis via multiple DNA repair pathways to maintain genome stability.
Article in The EMBO journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
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Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 69 citations in OpenAlex.
- Epigenome-wide association study of global cortical volumes in generation Scotland: Scottish family health study.Epigenetics · 2022Pooled it
- GCN5 and TADA2B constitutively regulate XRCC1 function during DNA repair to maintain cell survival.Cell death and differentiation · 2026Article
- Microcephaly, seizures and developmental delay caused by two novel mutations in theTranslational pediatrics · 2026Article
- Deficiency ofZoological research · 2026Article
- Fructose-2,6-bisphosphate restores TDP-43 pathology-driven genome repair deficiency in motor neuron diseases.Communications biology · 2026Article
- F2,6BP restores mitochondrial genome integrity in Huntington's disease.The Journal of biological chemistry · 2026Article
- B-cell immunodeficiency associated with polynucleotide kinase 3'-phosphatase (PNKP) deficiency.The journal of allergy and clinical immunology. Global · 2025Article
- Article
- Fructose-2,6-bisphosphate restores DNA repair activity of PNKP and ameliorates neurodegenerative symptoms in Huntington's disease.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Fructose-2,6-bisphosphate restores DNA repair activity of PNKP and ameliorates neurodegenerative symptoms in Huntington's disease.bioRxiv : the preprint server for biology · 2024Article
- DNA Damage Responses, the Trump Card of Stem Cells in the Survival Game.Advances in experimental medicine and biology · 2024Review
- Base Excision Repair: Mechanisms and Impact in Biology, Disease, and Medicine.International journal of molecular sciences · 2023Review
- DNA damage and repair: underlying mechanisms leading to microcephaly.Frontiers in cell and developmental biology · 2023Review
- Zika Virus Induces Mitotic Catastrophe in Human Neural Progenitors by Triggering Unscheduled Mitotic Entry in the Presence of DNA Damage While Functionally Depleting Nuclear PNKP.Journal of virology · 2022Article
- Mutations of the DNA repair gene PNKP in a patient with microcephaly, seizures, and developmental delay (MCSZ) presenting with a high-grade brain tumor.Scientific reports · 2022Article
- Polymerases and DNA Repair in Neurons: Implications in Neuronal Survival and Neurodegenerative Diseases.Frontiers in cellular neuroscience · 2022Review
- Prenatal phenotype of PNKP-related primary microcephaly associated with variants affecting both the FHA and phosphatase domain.European journal of human genetics : EJHG · 2022Article
- PNKP is required for maintaining the integrity of progenitor cell populations in adult mice.Life science alliance · 2021Article
- A Novel c.968C > T homozygous Mutation in the Polynucleotide Kinase 3' - Phosphatase Gene Related to the Syndrome of Microcephaly, Seizures, and Developmental Delay.Journal of pediatric genetics · 2021Article
- PIAS1 modulates striatal transcription, DNA damage repair, and SUMOylation with relevance to Huntington's disease.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Polynucleotide kinase-phosphatase (PNKP) is a DNA repair factor possessing both 5'-kinase and 3'-phosphatase activities to modify ends of a DNA break prior to ligation. Recently, decreased PNKP levels were identified as the cause of severe neuropathology present in the human microcephaly with seizures (MCSZ) syndrome. Utilizing novel murine Pnkp alleles that attenuate expression and a T424GfsX48 frame-shift allele identified in MCSZ individuals, we determined how PNKP inactivation impacts neurogenesis. Mice with PNKP inactivation in neural progenitors manifest neurodevelopmental abnormalities and postnatal death. This severe phenotype involved defective base excision repair and non-homologous end-joining, pathways required for repair of both DNA single- and double-strand breaks. Although mice homozygous for the T424GfsX48 allele were lethal embryonically, attenuated PNKP levels (akin to MCSZ) showed general neurodevelopmental defects, including microcephaly, indicating a critical developmental PNKP threshold. Directed postnatal neural inactivation of PNKP affected specific subpopulations including oligodendrocytes, indicating a broad requirement for genome maintenance, both during and after neurogenesis. These data illuminate the basis for selective neural vulnerability in DNA repair deficiency disease.
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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.