| Fructose-2,6-bisphosphate restores DNA repair activity of PNKP and ameliorates neurodegenerative symptoms in Huntington's disease. | Fructose-2,6-bisphosphate restores DNA repair activity of PNKP and ameliorates neurodegenerative symptoms in Huntington's disease.
Chakraborty A, Sreenivasmurthy SG, Miller W, Huai W, Biswas T, Mandal SM, Boscá L, Krishnan B, Ghosh G, Hazra T., | 09/25/2024 |
| Site-specific acetylation of polynucleotide kinase 3'-phosphatase regulates its distinct role in DNA repair pathways. | Site-specific acetylation of polynucleotide kinase 3'-phosphatase regulates its distinct role in DNA repair pathways.
Islam A, Chakraborty A, Sarker AH, Aryal UK, Pan L, Sharma G, Boldogh I, Hazra T., Free PMC Article | 03/25/2024 |
| Functional analysis of a conserved site mutation in the DNA end processing enzyme PNKP leading to ataxia with oculomotor apraxia type 4 in humans. | Functional analysis of a conserved site mutation in the DNA end processing enzyme PNKP leading to ataxia with oculomotor apraxia type 4 in humans.
Islam A, Chakraborty A, Gambardella S, Campopiano R, Sarker AH, Boldogh I, Hazra T., Free PMC Article | 06/2/2023 |
| 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. | 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.
Rychlowska M, Agyapong A, Weinfeld M, Schang LM., Free PMC Article | 05/21/2022 |
| Characteristics of epilepsy secondary to mutations in the PNKP gene. | Characteristics of epilepsy secondary to mutations in the PNKP gene.
Furones García M, Ortiz Cabrera NV, Soto Insuga V, García Peñas JJ. | 12/4/2021 |
| The Phenotypic Spectrum of PNKP-Associated Disease and the Absence of Immunodeficiency and Cancer Predisposition in a Dutch Cohort. | The Phenotypic Spectrum of PNKP-Associated Disease and the Absence of Immunodeficiency and Cancer Predisposition in a Dutch Cohort.
Garrelfs MR, Takada S, Kamsteeg EJ, Pegge S, Mancini G, Engelen M, van de Warrenburg B, Rennings A, van Gaalen J, Peters I, Weemaes C, van der Burg M, Willemsen MA. | 10/9/2021 |
| The FHA domain of PNKP is essential for its recruitment to DNA damage sites and maintenance of genome stability. | The FHA domain of PNKP is essential for its recruitment to DNA damage sites and maintenance of genome stability.
Tsukada K, Shimada M, Imamura R, Saikawa K, Ishiai M, Matsumoto Y. | 07/31/2021 |
| PIAS1 modulates striatal transcription, DNA damage repair, and SUMOylation with relevance to Huntington's disease. | PIAS1 modulates striatal transcription, DNA damage repair, and SUMOylation with relevance to Huntington's disease.
Morozko EL, Smith-Geater C, Monteys AM, Pradhan S, Lim RG, Langfelder P, Kachemov M, Kulkarni JA, Zaifman J, Hill A, Stocksdale JT, Cullis PR, Wu J, Ochaba J, Miramontes R, Chakraborty A, Hazra TK, Lau A, St-Cyr S, Orellana I, Kopan L, Wang KQ, Yeung S, Leavitt BR, Reidling JC, Yang XW, Steffan JS, Davidson BL, Sarkar PS, Thompson LM., Free PMC Article | 06/12/2021 |
| Mutational survivorship bias: The case of PNKP. | Mutational survivorship bias: The case of PNKP.
Bermúdez-Guzmán L, Jimenez-Huezo G, Arguedas A, Leal A., Free PMC Article | 01/16/2021 |
| Pathological mutations in PNKP trigger defects in DNA single-strand break repair but not DNA double-strand break repair. | Pathological mutations in PNKP trigger defects in DNA single-strand break repair but not DNA double-strand break repair.
Kalasova I, Hailstone R, Bublitz J, Bogantes J, Hofmann W, Leal A, Hanzlikova H, Caldecott KW., Free PMC Article | 09/12/2020 |
| Study provides evidence that wild-type ATXN3 plays an important role in error-free repair of DNA double-strand breaks in the transcribed genes. In contrast, mutant ATXN3 blocks the activity of a DNA end-processing enzyme, polynucleotide kinase 3'-phosphatase (PNKP), leading to progressive accumulation of double-strand breaks and abrogation of global transcription. | Deficiency in classical nonhomologous end-joining-mediated repair of transcribed genes is linked to SCA3 pathogenesis.
Chakraborty A, Tapryal N, Venkova T, Mitra J, Vasquez V, Sarker AH, Duarte-Silva S, Huai W, Ashizawa T, Ghosh G, Maciel P, Sarkar PS, Hegde ML, Chen X, Hazra TK., Free PMC Article | 07/25/2020 |
| The authors report that HTT forms a transcription-coupled DNA repair (TCR) complex with RNA polymerase II subunit A (POLR2A), ataxin-3, the DNA repair enzyme polynucleotide-kinase-3'-phosphatase (PNKP), and cyclic AMP-response element-binding (CREB) protein (CBP). This complex senses and facilitates DNA damage repair during transcriptional elongation, but its functional integrity is impaired by mutant HTT. | Mutant huntingtin impairs PNKP and ATXN3, disrupting DNA repair and transcription.
Gao R, Chakraborty A, Geater C, Pradhan S, Gordon KL, Snowden J, Yuan S, Dickey AS, Choudhary S, Ashizawa T, Ellerby LM, La Spada AR, Thompson LM, Hazra TK, Sarkar PS., Free PMC Article | 02/29/2020 |
| Our results may hence improve the understanding of the mechanisms associated with DNA repair and fetaldevelopment in PNKP-associated disorders. | Two patients with PNKP mutations presenting with microcephaly, seizure, and oculomotor apraxia.
Taniguchi-Ikeda M, Morisada N, Inagaki H, Ouchi Y, Takami Y, Tachikawa M, Satake W, Kobayashi K, Tsuneishi S, Takada S, Yamaguchi H, Nagase H, Nozu K, Okamoto N, Nishio H, Toda T, Morioka I, Wada H, Kurahashi H, Iijima K. | 10/5/2019 |
| PKNP variants are the major causative variant for the Charcot-Marie-Tooth disease CMT2 phenotype in these individuals and that the milder clinical manifestation is due to an allelic effect. | The polynucleotide kinase 3'-phosphatase gene (PNKP) is involved in Charcot-Marie-Tooth disease (CMT2B2) previously related to MED25.
Leal A, Bogantes-Ledezma S, Ekici AB, Uebe S, Thiel CT, Sticht H, Berghoff M, Berghoff C, Morera B, Meisterernst M, Reis A., Free PMC Article | 09/28/2019 |
| This study found that an XRCC1 fragment, comprising residues 166-436, binds tightly to PNKP and DNA and efficiently activates PNKP's kinase activity. | Domain analysis of PNKP-XRCC1 interactions: Influence of genetic variants of XRCC1.
Mani RS, Mermershtain I, Abdou I, Fanta M, Hendzel MJ, Glover JNM, Weinfeld M., Free PMC Article | 05/4/2019 |
| Study reports a novel missense variant c.1133A>C (p.Lys378Thr) on the 13th exon of PNKP gene identified by whole exome sequencing in an Iranian multi-affected family with microcephaly, seizures and developmental delay disorder. | Multi affected pedigree with congenital microcephaly: WES revealed PNKP gene mutation.
Entezam M, Razipour M, Talebi S, Beiraghi Toosi M, Keramatipour M. | 05/4/2019 |
| Despite presence of an alternative 3'-phosphatase, loss of PNKP significantly sensitizes cells to 3'-phosphate-terminated DSBs, due to a 3'-dephosphorylation defect. | Persistent 3'-phosphate termini and increased cytotoxicity of radiomimetic DNA double-strand breaks in cells lacking polynucleotide kinase/phosphatase despite presence of an alternative 3'-phosphatase.
Chalasani SL, Kawale AS, Akopiants K, Yu Y, Fanta M, Weinfeld M, Povirk LF., Free PMC Article | 10/6/2018 |
| PNKP mutation in two siblings is associated with progressive ataxia, abnormal saccades, sensorimotor neuropathy and dystonia consistent with ataxia with oculomotor apraxia disorders. | Novel PNKP mutation in siblings with ataxia-oculomotor apraxia type 4.
Schiess N, Zee DS, Siddiqui KA, Szolics M, El-Hattab AW. | 03/17/2018 |
| we have identified a mutation in PNKP, leading to a phenotype of microcephaly with primordial dwarfism. | Microcephalic primordial dwarfism in an Emirati patient with PNKP mutation.
Nair P, Hamzeh AR, Mohamed M, Saif F, Tawfiq N, El Halik M, Al-Ali MT, Bastaki F. | 10/28/2017 |
| XRCC1 and PNKP interact via a high-affinity phosphorylation-dependent interaction site in XRCC1 and a forkhead-associated domain in PNKP. Data suggest a second PNKP interaction site in XRCC1 that binds PNKP with lower affinity and independently of XRCC1 phosphorylation. (XRCC1 = X-ray repair cross complementing protein 1; PNKP = polynucleotide kinase 3'-phosphatase) | The Rev1 interacting region (RIR) motif in the scaffold protein XRCC1 mediates a low-affinity interaction with polynucleotide kinase/phosphatase (PNKP) during DNA single-strand break repair.
Breslin C, Mani RS, Fanta M, Hoch N, Weinfeld M, Caldecott KW., Free PMC Article | 10/21/2017 |
| In a recombinant PNKP-XRCC4-LigIV complex, stable binding of PNKP requires XRCC4 phosphorylation. Only one PNKP protomer binds per XRCC4 dimer. Both the PNKP FHA and catalytic domains contact the XRCC4 coiled-coil and LigIV BRCT repeats. A surface on the PNKP phosphatase domain may contact XRCC4-LigIV. A mutation on this surface (E326K) impairs PNKP recruitment to damaged DNA and causes microcephaly with seizures. | Structural and functional characterization of the PNKP-XRCC4-LigIV DNA repair complex.
Aceytuno RD, Piett CG, Havali-Shahriari Z, Edwards RA, Rey M, Ye R, Javed F, Fang S, Mani R, Weinfeld M, Hammel M, Tainer JA, Schriemer DC, Lees-Miller SP, Glover JNM., Free PMC Article | 10/7/2017 |
| Mutations in TDP1 and APTX have been linked to Spinocerebellar ataxia with axonal neuropathy (SCAN1) and Ataxia-ocular motor apraxia 1 (AOA1), respectively, while mutations in PNKP are considered to be responsible for Microcephaly with seizures (MCSZ) and Ataxia-ocular motor apraxia 4 (AOA4). | Neurological disorders associated with DNA strand-break processing enzymes.
Jiang B, Glover JN, Weinfeld M., Free PMC Article | 08/12/2017 |
| the role for PNKP in maintaining brain function and how perturbation in its activity can account for the varied pathology of neurodegeneration or microcephaly present in microcephaly with seizures and ataxia with oculomotor apraxia 4 respectively. | Polynucleotide kinase-phosphatase (PNKP) mutations and neurologic disease.
Dumitrache LC, McKinnon PJ., Free PMC Article | 08/12/2017 |
| In 11 Portuguese patients, PNKP mutations cause ataxia with oculomotor apraxia type 4. | Hot topic: PNKP mutations cause ataxia with oculomotor apraxia type 4.
Balint B, Bhatia KP. | 01/28/2017 |
| Here we report that purified wild-type (WT) ATXN3 stimulates, and by contrast the mutant form specifically inhibits, PNKP's 3' phosphatase activity in vitro. ATXN3-deficient cells also show decreased PNKP activity | The role of the mammalian DNA end-processing enzyme polynucleotide kinase 3'-phosphatase in spinocerebellar ataxia type 3 pathogenesis.
Chatterjee A, Saha S, Chakraborty A, Silva-Fernandes A, Mandal SM, Neves-Carvalho A, Liu Y, Pandita RK, Hegde ML, Hegde PM, Boldogh I, Ashizawa T, Koeppen AH, Pandita TK, Maciel P, Sarkar PS, Hazra TK., Free PMC Article | 08/8/2015 |