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    GENE:

    MDC1 (Mediator Of DNA Damage Checkpoint 1)

    i
    Other names: MDC1, Mediator Of DNA Damage Checkpoint 1, NFBD1, Mediator Of DNA Damage Checkpoint Protein 1, Nuclear Factor With BRCT Domains 1, KIAA0170, Homologue To Drosophila Photoreceptor Protein Calphotin, Mediator Of DNA-Damage Checkpoint 1, Em:AB023051.5
    7d
    Ononin Sensitizes Papillary Thyroid Carcinoma Cells to Cisplatin by Repressing DNA Damage Response via E2F2. (PubMed, Int J Endocrinol)
    Functional assays confirm that ononin-induced repression of E2F2 impairs DNA repair capacity and increases cisplatin sensitivity in cisplatin-resistant PTC cells. These findings identify ononin as a promising adjuvant candidate for overcoming cisplatin resistance in PTC by targeting the E2F2/MDC1-dependent DDR pathway.
    Journal
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    MDC1 (Mediator Of DNA Damage Checkpoint 1) • E2F2 (E2F Transcription Factor 2)
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    cisplatin
    5ms
    RAD51 is chromatin enriched and targetable in BRCA1-deficient cells. (PubMed, Mol Cell)
    Unlike 53BP1 loss, however, loss of MDC1 and H2AX in BRCA1-deficient cells does not restore RAD51 foci, further uncoupling HR from PARPi resistance. Collectively, we propose a model in which ssDNA gaps in BRCA1-deficient cells necessitate post-replicative RAD51 chromatin engagement for cell fitness, diverting RAD51 from other roles and revealing a targetable vulnerability.
    Journal • BRCA Biomarker • PARP Biomarker
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    BRCA1 (Breast cancer 1, early onset) • RAD51 (RAD51 Homolog A) • MDC1 (Mediator Of DNA Damage Checkpoint 1) • TP53BP1 (Tumor Protein P53 Binding Protein 1)
    almost2years
    Prediction of deleterious non-synonymous SNPs of human MDC1 gene: an in silico approach. (PubMed, Syst Biol Reprod Med)
    The present study concludes that the highly deleterious P194R mutations can potentially induce genomic instability and contribute to various cancers' pathogenesis. Developing drugs targeting these mutations can undoubtedly be advantageous in large population-based studies, particularly in the development of precision medicine.
    Journal
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    MDC1 (Mediator Of DNA Damage Checkpoint 1)
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    MDC1 mutation
    almost2years
    Correlation analysis between peripheral blood dendritic cell subsets and PD-1 in patients with peritoneal adenocarcinoma. (PubMed, Braz J Med Biol Res)
    Our results revealed that DCs subsets correlated with peritoneal adenocarcinoma malignancy. Dendritic cells play an independent role in the immune function of peritoneal adenocarcinoma.
    Journal
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    CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • MDC1 (Mediator Of DNA Damage Checkpoint 1)
    over2years
    Impact of programmed death-ligand 1 (PD-L1) positivity on clinical and molecular features of patients with metastatic gastric cancer. (PubMed, Cancer Med)
    PD-L1 expression is an independent and sensitive biomarker for ICI therapy. Considering its significant association with several gene alterations, including PIK3CA mutations and MET amplification, combining ICI therapy with other targeted agents may be a promising therapeutic strategy for GC.
    Journal • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker • Metastases
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    PD-L1 (Programmed death ligand 1) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • MET (MET proto-oncogene, receptor tyrosine kinase) • MSI (Microsatellite instability) • TET2 (Tet Methylcytosine Dioxygenase 2) • LRP1B (LDL Receptor Related Protein 1B) • IRS2 (Insulin receptor substrate 2) • PTPRT (Protein tyrosine phosphatase receptor type T) • DOT1L (DOT1 Like Histone Lysine Methyltransferase) • MDC1 (Mediator Of DNA Damage Checkpoint 1)
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    PD-L1 expression • TMB-H • PIK3CA mutation • MET amplification • TET2 mutation • MET mutation • MDC1 mutation
    almost3years
    A positive feedback loop between ID3 and PPARγ via DNA damage repair regulates the efficacy of radiotherapy for rectal cancer. (PubMed, BMC Cancer)
    ID3 and PPARγ influence the radiosensitivity of colorectal cancer cells by interacting with MDC1 to form a positive feedback loop that promotes DNA damage repair. Patients with low expression of ID3 who received neoadjuvant chemoradiotherapy can obtain a better curative effect.
    Journal
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    PPARG (Peroxisome Proliferator Activated Receptor Gamma) • ID3 (Inhibitor Of DNA Binding 3, HLH Protein) • MDC1 (Mediator Of DNA Damage Checkpoint 1)
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    ID3 underexpression
    over3years
    Targeting MDC1 promotes apoptosis and sensitizes Imatinib resistance in CML cells by mainly disrupting non-homologous end-joining repair. (PubMed, Med Oncol)
    Our work revealed that MDC1 is a prospective target for CML treatment through regulating DNA damage repair mechanism, and also an alternative option for IM resistance dilemma. This study extends the understanding of regulating dysfunctional DNA repair mechanisms for cancer treatment.
    Journal
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    MDC1 (Mediator Of DNA Damage Checkpoint 1) • TP53BP1 (Tumor Protein P53 Binding Protein 1)
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    imatinib
    over3years
    AP4 suppresses DNA damage, chromosomal instability and senescence via inducing MDC1/Mediator of DNA damage Checkpoint 1 and repressing MIR22HG/miR-22-3p. (PubMed, Mol Cancer)
    In summary, AP4, miR-22-3p and MDC1 form a conserved and coherent, regulatory feed-forward loop to promote DNA repair, which suppresses DNA damage, senescence and CIN, and contributes to 5-FU resistance. These findings explain how elevated AP4 expression contributes to development and chemo-resistance of colorectal cancer after c-MYC activation.
    Journal
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    MYC (V-myc avian myelocytomatosis viral oncogene homolog) • MDC1 (Mediator Of DNA Damage Checkpoint 1) • MIR22 (MicroRNA 22) • MIR22HG (MIR22 Host Gene)
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    MYC expression
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    5-fluorouracil