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Last update 08 May 2025

POLI

Last update 08 May 2025

Basic Info

Synonyms

DNA polymerase iota, Eta2, POLI

+ [3]

Introduction

Error-prone DNA polymerase specifically involved in DNA repair (PubMed:11013228, PubMed:11387224). Plays an important role in translesion synthesis, where the normal high-fidelity DNA polymerases cannot proceed and DNA synthesis stalls (PubMed:11013228, PubMed:11387224, PubMed:14630940, PubMed:15199127). Favors Hoogsteen base-pairing in the active site (PubMed:15254543). Inserts the correct base with high-fidelity opposite an adenosine template (PubMed:15254543). Exhibits low fidelity and efficiency opposite a thymidine template, where it will preferentially insert guanosine (PubMed:11013228). May play a role in hypermutation of immunoglobulin genes (PubMed:12410315). Forms a Schiff base with 5'-deoxyribose phosphate at abasic sites, but may not have lyase activity (PubMed:11251121, PubMed:14630940).

Drugs associated with POLI

OPV2-c1

Target

POLI

Mechanism

POLI inhibitors

Active Org.-

Originator Org.

PT Bio Farma

Active Indication-

Inactive Indication

Poliomyelitis

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with POLI

100 Translational Medicine associated with POLI

0 Patents (Medical) associated with POLI

183

Literatures (Medical) associated with POLI

01 Jun 2025·Journal of Translational Autoimmunity

Cross-tissue transcriptome-wide association study reveals novel psoriasis susceptibility genes

Article

Author: Huang, Zongju ; Liu, Jie ; Yan, Fei ; Tao, Jing ; Chen, Yongliang

BackgroundPsoriasis is a chronic, immune-mediated inflammatory skin disorder with a strong genetic component. Although numerous GWAS have identified risk loci, many associated variants lie in non-coding regions, complicating functional interpretation.ObjectiveThis study aimed to identify novel psoriasis susceptibility genes by integrating large-scale GWAS and eQTL data using a cross-tissue TWAS approach.MethodsWe integrated psoriasis GWAS summary statistics from the FinnGen database with GTEx V8 eQTL data. A cross-tissue TWAS was performed using UTMOST, followed by validation with single-tissue TWAS via FUSION. Conditional and joint analyses were conducted to delineate independent genetic signals, and gene-based analysis was performed using MAGMA. Causal relationships were evaluated using Mendelian randomization (MR) and Bayesian colocalization analyses. Key SNPs were functionally characterized using CADD, GERP++, and RegulomeDB for pathogenicity prediction and regulatory potential assessment. Finally, functional network analysis was conducted using GeneMANIA.ResultsThe cross-tissue TWAS identified 259 genes significantly associated with psoriasis (p < 0.05), with 12 remaining significant after FDR correction. Single-tissue TWAS validation revealed 655 significant genes, with an overlap of three protein-coding candidates: POLI, NFKB1, and ZFYVE28. Cross-validation with MAGMA refined the candidate set to NFKB1 and ZFYVE28. MR and colocalization analyses supported a causal relationship for NFKB1 in Skeletal Muscle, Transverse Colon, and Cultured Fibroblasts, and for ZFYVE28 in Subcutaneous Adipose Tissue and Esophageal Mucosa tissues. Functional annotation identified key SNPs including rs4235405, rs3774960, and rs1598856 for NFKB1, and rs1203786 for ZFYVE28, with varying degrees of pathogenicity and regulatory potential. GeneMANIA network analysis further implicated NFKB1 in NF-κB signaling and ZFYVE28 in vesicle-mediated transport.ConclusionOur integrative multi-omics approach identifies NFKB1 and ZFYVE28 as novel psoriasis susceptibility genes, providing potential biomarkers and therapeutic targets for this complex disease.

01 Sep 2024·DNA Repair

Human translesion DNA polymerases ι and κ mediate tolerance to temozolomide in MGMT-deficient glioblastoma cells.

Article

Author: Leandro, Giovana da Silva ; Bastos, André Uchimura ; Hoch, Nicolas Carlos ; Ashton, Nicholas William ; Woodgate, Roger ; Moreno, Natália Cestari ; Menck, Carlos Frederico Martins ; Martins, Davi Jardim ; Ribeiro, Victória Chaves ; Rocha, Clarissa Ribeiro Reily ; Latancia, Marcela Teatin ; Ariwoola, Abu-Bakr Adetayo

Glioblastoma (GBM) is a highly aggressive brain tumor associated with poor patient survival. The current standard treatment involves invasive surgery, radiotherapy, and chemotherapy employing temozolomide (TMZ). Resistance to TMZ is, however, a major challenge. Previous work from our group has identified candidate genes linked to TMZ resistance, including genes encoding translesion synthesis (TLS) DNA polymerases iota (Polɩ) and kappa (Polκ). These specialized enzymes are known for bypassing lesions and tolerating DNA damage. Here, we investigated the roles of Polɩ and Polκ in TMZ resistance, employing MGMT-deficient U251-MG glioblastoma cells, with knockout of either POLI or POLK genes encoding Polɩ and Polκ, respectively, and assess their viability and genotoxic stress responses upon subsequent TMZ treatment. Cells lacking either of these polymerases exhibited a significant decrease in viability following TMZ treatment compared to parental counterparts. The restoration of the missing polymerase led to a recovery of cell viability. Furthermore, knockout cells displayed increased cell cycle arrest, mainly in late S-phase, and lower levels of genotoxic stress after TMZ treatment, as assessed by a reduction of γH2AX foci and flow cytometry data. This implies that TMZ treatment does not trigger a significant H2AX phosphorylation response in the absence of these proteins. Interestingly, combining TMZ with Mirin (double-strand break repair pathway inhibitor) further reduced the cell viability and increased DNA damage and γH2AX positive cells in TLS KO cells, but not in parental cells. These findings underscore the crucial roles of Polɩ and Polκ in conferring TMZ resistance and the potential backup role of homologous recombination in the absence of these TLS polymerases. Targeting these TLS enzymes, along with double-strand break DNA repair inhibition, could, therefore, provide a promising strategy to enhance TMZ's effectiveness in treating GBM.

01 Feb 2024·Molecular Biology and Evolution

Encyclopedia of Family A DNA Polymerases Localized in Organelles: Evolutionary Contribution of Bacteria Including the Proto-Mitochondrion

Article

Author: Yazaki, Euki ; Kim, Eunsoo ; Hirakawa, Yoshihisa ; Inagaki, Yuji ; Eliáš, Marek ; Nakano, Kentaro ; Harada, Ryo ; Kamikawa, Ryoma ; Yabuki, Akinori

AbstractDNA polymerases synthesize DNA from deoxyribonucleotides in a semiconservative manner and serve as the core of DNA replication and repair machinery. In eukaryotic cells, there are 2 genome-containing organelles, mitochondria, and plastids, which were derived from an alphaproteobacterium and a cyanobacterium, respectively. Except for rare cases of genome-lacking mitochondria and plastids, both organelles must be served by nucleus-encoded DNA polymerases that localize and work in them to maintain their genomes. The evolution of organellar DNA polymerases has yet to be fully understood because of 2 unsettled issues. First, the diversity of organellar DNA polymerases has not been elucidated in the full spectrum of eukaryotes. Second, it is unclear when the DNA polymerases that were used originally in the endosymbiotic bacteria giving rise to mitochondria and plastids were discarded, as the organellar DNA polymerases known to date show no phylogenetic affinity to those of the extant alphaproteobacteria or cyanobacteria. In this study, we identified from diverse eukaryotes 134 family A DNA polymerase sequences, which were classified into 10 novel types, and explored their evolutionary origins. The subcellular localizations of selected DNA polymerases were further examined experimentally. The results presented here suggest that the diversity of organellar DNA polymerases has been shaped by multiple transfers of the PolI gene from phylogenetically broad bacteria, and their occurrence in eukaryotes was additionally impacted by secondary plastid endosymbioses. Finally, we propose that the last eukaryotic common ancestor may have possessed 2 mitochondrial DNA polymerases, POP, and a candidate of the direct descendant of the proto-mitochondrial DNA polymerase I, rdxPolA, identified in this study.

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