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    GENE:

    POLE4 (DNA Polymerase Epsilon 4 Accessory Subunit)

    i
    Other names: POLE4, DNA Polymerase Epsilon 4 Accessory Subunit, Polymerase (DNA) Epsilon 4 Accessory Subunit, DNA Polymerase Epsilon Subunit P12, DNA Polymerase Epsilon Subunit 4, DNA Polymerase II Subunit 4, Polymerase (DNA-Directed) Epsilon 4 Accessory Subunit, Polymerase (DNA-Directed) Epsilon 4 (P12 Subunit), YHHQ1, P12
    4ms
    Genetic and Functional Evidence Links Germline Biallelic Inactivating Variants in WWOX to Histological Mixed-Type Thyroid Cancer. (PubMed, Adv Sci (Weinh))
    Finally, low WWOX expression is found to be associated with epithelial-mesenchymal transition and aggressive phenotype in thyroid cancer. These findings provide the first genetic and functional evidence that germline WWOX loss-of-function variants drive cancer pathogenesis by perturbing multiple tumor-suppressive mechanisms.
    Journal
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    POLE4 (DNA Polymerase Epsilon 4 Accessory Subunit) • WWOX (WW Domain Containing Oxidoreductase)
    6ms
    Unveiling Replication Timing-Dependent Mutational Biases: Mechanistic Insights from Gene Knockouts and Genotoxins Exposures. (PubMed, Int J Mol Sci)
    Our systematic bioinformatics approach identifies new DNA repair genes and mutagens that exhibit differential activity during the S phase. These findings pave the way for further investigation of factors that contribute to genome instability during cancer transformation.
    Journal • PARP Biomarker
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    TP53 (Tumor protein P53) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • PARP1 (Poly(ADP-Ribose) Polymerase 1) • PMS1 (PMS1 protein homolog 1) • POLE4 (DNA Polymerase Epsilon 4 Accessory Subunit) • POLG2 (DNA Polymerase Gamma 2, Accessory Subunit) • PRKDC (Protein Kinase, DNA-Activated, Catalytic Subunit)
    9ms
    Knockout of SIN3B modulates transcriptional programs and cell survival in cutaneous melanoma. (PubMed, Pharmacol Res)
    Moreover, pooled genome-wide CRISPR/Cas9 screens highlighted POLE4 and STK11 as crucial for the fitness and survival of SIN3B-knockout melanoma cells suggesting a role for these genes in epistasis with SIN3B. In summary, our findings suggest that SIN3B plays a pivotal role in modulating the behavior of melanoma cells, with implications for tumor growth and response to therapy.
    Journal
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    BRAF (B-raf proto-oncogene) • STK11 (Serine/threonine kinase 11) • POLE4 (DNA Polymerase Epsilon 4 Accessory Subunit)
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    BRAF mutation
    11ms
    The identification and prediction of lung adenocarcinoma prognosis using a novel gene signature associated with DNA replication. (PubMed, Transl Cancer Res)
    An innovative signature related to DNA replication was found to be a good prognostic predictor of LUAD. Our findings may provide novel insights into the diagnosis and treatment of LUAD.
    Journal • Gene Signature • PD(L)-1 Biomarker • IO biomarker
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    PD-L1 (Programmed death ligand 1) • CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • LAG3 (Lymphocyte Activating 3) • PD-L2 (Programmed Cell Death 1 Ligand 2) • POLD1 (DNA Polymerase Delta 1) • PCNA (Proliferating cell nuclear antigen) • POLD2 (DNA Polymerase Delta 2) • MCM4 (Minichromosome Maintenance Complex Component 4) • POLE4 (DNA Polymerase Epsilon 4 Accessory Subunit) • SIGLEC15 (Sialic Acid Binding Ig Like Lectin 15) • FEN1 (Flap Structure-Specific Endonuclease 1) • MCM2 (Minichromosome maintenance complex component 2) • MCM5 (Minichromosome Maintenance Complex Component 5) • MCM7 (Minichromosome Maintenance Complex Component 7) • RPA3 (Replication Protein A3) • MCM6 (Minichromosome Maintenance Complex Component 6) • POLA2 (DNA Polymerase Alpha 2)
    almost2years
    Loss of POLE3-POLE4 unleashes replicative gap accumulation upon treatment with PARP inhibitors. (PubMed, Cell Rep)
    In addition to this, the loss of POLE3-POLE4 further sensitizes BRCA1-silenced cells to PARPis. Importantly, the knockdown of 53BP1 does not rescue PARPi sensitivity in POLE3-POLE4 KO cells, bypassing a common PARPi resistance mechanism and outlining a potential strategy to sensitize cancer cells to PARPis.
    Journal • BRCA Biomarker • PARP Biomarker
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RAD51 (RAD51 Homolog A) • POLE4 (DNA Polymerase Epsilon 4 Accessory Subunit) • TP53BP1 (Tumor Protein P53 Binding Protein 1)
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    BRCA2 mutation • BRCA1 mutation
    almost2years
    TET3 gene rs828867 G>A polymorphism reduces neuroblastoma risk in Chinese children. (PubMed, Heliyon)
    GTEx analysis suggested that rs828867 G > A was significantly associated with RP11-287D1.4 and POLE4 mRNA expression. Overall, our results revealed that rs828867 G > A in the TET3 gene is significantly associated with predisposition to NB.
    Journal
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    POLE4 (DNA Polymerase Epsilon 4 Accessory Subunit) • TET3 (Tet Methylcytosine Dioxygenase 3)
    over2years
    Asymmetric distribution of parental H3K9me3 in S phase silences L1 elements. (PubMed, Nature)
    Similar results were obtained in cells expressing a MPP8 mutant defective in H3K9me3 binding and in TASOR mutants with reduced interactions with Pol ε. These results reveal an unexpected mechanism whereby the HUSH complex functions with Pol ε to promote asymmetric H3K9me3 distribution at head-on LINEs to suppress their expression in S phase.
    Journal
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    POLE4 (DNA Polymerase Epsilon 4 Accessory Subunit)
    over2years
    Identification of DNA damage response-related genes as biomarkers for castration-resistant prostate cancer. (PubMed, Sci Rep)
    Thus, our study suggests that six DDR-related genes would be important for Pca progression. RFC2 could be a useful biomarker associated with poor outcomes of patients with Pca.
    Journal
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    POLD1 (DNA Polymerase Delta 1) • LRIG1 (Leucine Rich Repeats And Immunoglobulin Like Domains 1) • POLE4 (DNA Polymerase Epsilon 4 Accessory Subunit) • RFC4 (Replication Factor C Subunit 4)
    over2years
    Molecular landscapes of glioblastoma cell lines revealed a group of patients that do not benefit from WWOX tumor suppressor expression. (PubMed, Front Neurosci)
    Among these patients, WWOX may be inaccessible for its partners and does not manifest its anti-cancer activity, which was proposed in the literature but not regarding glioblastoma or concerning POLE4 and HSF2BP. Cell lines data enabled the identification of patients among which, despite high expression of WWOX tumor suppressor, no advantageous outcomes were noted due to the cancer-promoting profile ensured by other genes.
    Preclinical • Journal
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    POLE4 (DNA Polymerase Epsilon 4 Accessory Subunit) • WWOX (WW Domain Containing Oxidoreductase)
    almost3years
    Somatic Variants in DNA Damage Response Genes in Ovarian Cancer Patients Using Whole-exome Sequencing. (PubMed, Anticancer Res)
    As the identified variants were not only limited to well-known TP53, BRCA1/2, and HR-associated genes, our study might contribute to the better understanding of which DDR pathways potentially influence disease progression. Moreover, they may display a potential role as biomarkers to predict platinum-based chemotherapy or PARPi treatment response or disease progression, as differences in disrupted DDR pathways were observed between patients with long and short overall survival in HGSC and oCCC groups.
    Journal • BRCA Biomarker • PARP Biomarker
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    TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • ERCC3 (ERCC Excision Repair 3, TFIIH Core Complex Helicase Subunit) • POLE4 (DNA Polymerase Epsilon 4 Accessory Subunit) • RPA3 (Replication Protein A3)
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    HRD
    almost5years
    Novel LRRK2 mutations and other rare, non-BAP1-related candidate tumor predisposition gene variants in high-risk cancer families with mesothelioma and other tumors. (PubMed, Hum Mol Genet)
    Affected genes encode proteins involved in DNA repair (ATM, ATR, BRCA2, BRIP1, CHEK2, MLH3, MUTYH, POLE, POLE4, POLQ, XRCC1), chromatin modification (ARID1B, DNMT3A, JARID2, SETD1B) or other cellular pathways: LRRK2 (2 cases) and MSH4. Notably, somatic truncating mutation or deletions of LRRK2 were occasionally found in MMs in The Cancer Genome Atlas, and expression of LRRK2 was undetectable or downregulated in a majority of primary MMs and MM cell lines we examined, implying that loss of LRRK2 expression is a newly recognized tumor suppressor alteration in MM.
    Journal • BRCA Biomarker
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    BRCA2 (Breast cancer 2, early onset) • DNMT3A (DNA methyltransferase 1) • BAP1 (BRCA1 Associated Protein 1) • CHEK2 (Checkpoint kinase 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • ARID1B (AT-Rich Interaction Domain 1B) • MUTYH (MutY homolog) • MSH4 (MutS Homolog 4) • POLE4 (DNA Polymerase Epsilon 4 Accessory Subunit) • XRCC1 (X-Ray Repair Cross Complementing 1)
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    BAP1 mutation • CHEK2 mutation • BRIP1 mutation • MLH3 mutation
    5years
    Role of Amygdalin in Blocking DNA Replication in Breast Cancer In Vitro. (PubMed, Curr Pharm Biotechnol)
    Amygdalin treatment caused downregulation of several genes that play critical roles in DNA replication in the MCF-7 cell line. Thus, it might be useful as an anticancer agent.
    Preclinical • Journal
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    PCNA (Proliferating cell nuclear antigen) • LRIG1 (Leucine Rich Repeats And Immunoglobulin Like Domains 1) • POLE4 (DNA Polymerase Epsilon 4 Accessory Subunit) • MCM2 (Minichromosome maintenance complex component 2) • MCM3 (Minichromosome maintenance complex component 3) • MCM5 (Minichromosome Maintenance Complex Component 5)