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    GENE:

    FANCD2 (FA Complementation Group D2)

    i
    Other names: FANCD2, FA Complementation Group D2, FA-D2, FACD, FAD, Fanconi Anemia Complementation Group D2, Fanconi Anemia Group D2 Protein, FANCD, Protein FACD2, FAD2, FA4
    2d
    A comprehensive genomic framework for identifying genes predisposing to homologous recombination repair-deficient breast or ovarian cancer. (PubMed, BJC Rep)
    Our approach provides a framework for the identification of candidate HRD-related CSGs through combined statistical and clinico-genomics analyses. It is adaptable to other mutational signatures/cancer types and will be most effective when applied to larger and well-annotated datasets.
    Journal • BRCA Biomarker
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • BRCA (Breast cancer early onset) • RAD51B (RAD51 Paralog B) • FANCD2 (FA Complementation Group D2)
    1m
    Synergistic Cellular Toxicity from Inhibition of Poly(ADP-ribose) Glycohydrolase (PARG) and Ubiquitin-Specific Protease 1 (USP1). (PubMed, Toxics)
    Using cell cytotoxicity, synergy, PCNA-ubiquitin, and PAR analyses, it is demonstrated herein that PARG inhibition, combined with USP1 inhibition, leads to increased levels of mono-ubiquitinated PCNA, decreased PAR accumulation, and synergistic cytotoxicity between ML323, a potent USP1i, and PDD00017273, a model PARGi. Future studies will focus on the mechanism that contributes to USP1/PARG synthetic lethality, the mechanism of cell death, and the impact of USP1 on PAR/ubiquitin dynamics and replication stress signaling.
    Journal • BRCA Biomarker • PARP Biomarker
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PCNA (Proliferating cell nuclear antigen) • FANCD2 (FA Complementation Group D2) • USP1 (Ubiquitin Specific Peptidase 1)
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    BRCA2 mutation • BRCA1 mutation
    2ms
    PARPi-PANC: Niraparib as First Line Therapy With Metastatic Homologous Repair-deficient Pancreatic Cancer (clinicaltrials.gov)
    P2, N=2, Terminated, Centre Leon Berard | Withdrawn --> Terminated; Study not feasible, patient accrual rate too low.
    Trial termination
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha) • FANCD2 (FA Complementation Group D2)
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    Zejula (niraparib)
    2ms
    SLC1A5-mediated kynurenine metabolism drives AHR-FANCD2 axis to remodel chromatin and induce T cell exhaustion in lung adenocarcinoma. (PubMed, Cell Commun Signal)
    This study suggests that SLC1A5 is upregulated in TEX, which modulates kynurenine metabolism and induces T cell exhaustion through the AHR-FANCD2 axis-mediated chromatin remodeling.
    Journal
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    CD8 (cluster of differentiation 8) • SLC1A5 (Solute Carrier Family 1 Member 5) • FANCD2 (FA Complementation Group D2)
    2ms
    Integrative single-cell transcriptomic and multi-dimensional bioinformatic analysis reveals proliferation-associated gene expression signatures and cellular heterogeneity in hepatocellular carcinoma. (PubMed, Discov Oncol)
    This integrative multi-scale analysis reveals complex proliferation-associated gene expression patterns and substantial cellular heterogeneity within hepatocellular carcinoma. STMN1 and RRM2 emerge as dominant markers of proliferative reprogramming and promising candidate therapeutic targets warranting further functional investigation in HCC progression.
    Journal
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    AURKA (Aurora kinase A) • RRM2 (Ribonucleotide Reductase Regulatory Subunit M2) • FANCD2 (FA Complementation Group D2) • STMN1 (Stathmin 1)
    2ms
    FANCD2 restrains fork progression and prevents fragility at early origins upon re-replication. (PubMed, Nat Commun)
    Importantly, reducing transcription and R-loops alleviates re-replication-induced genome fragility, whereas PARP inhibition exacerbates it. Our study uncovers a role for FANCD2 in safeguarding genome integrity during re-replication, offering avenues for selective targeting of cancer cells.
    Journal
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    FANCD2 (FA Complementation Group D2)
    2ms
    Main Genes Linked to the Immune Microenvironment in High-Grade Serous Ovarian Cancer. (PubMed, Adv Biomed Res)
    The current study recognized the most relevant genes involved in the immune system in high-grade serous ovarian cancer. The findings of this study provided a holistic understanding of the tumor microenvironment that can be used for introducing therapeutic targets.
    Journal • IO biomarker
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    IGF2BP1 (Insulin Like Growth Factor 2 MRNA Binding Protein 1) • FANCD2 (FA Complementation Group D2) • PTPN22 (Protein Tyrosine Phosphatase Non-Receptor Type 22) • STAT4 (Signal Transducer And Activator Of Transcription 4) • CD3E (CD3 Epsilon Subunit Of T-Cell Receptor Complex)
    3ms
    CRISPR/Cas9-based genome-wide screen reveals a synergistic effect of Irinotecan and USP1 inhibitor in colorectal cancer. (PubMed, Eur J Pharmacol)
    RNA sequencing further highlighted the enrichment of cAMP, PI3K-AKT, and Wnt pathways, which are all linked to CREB activity in the combination group. These findings establish USP1 inhibition as a promising strategy to overcome Irinotecan resistance through the combination strategy, providing a novel therapeutic avenue for CRC.
    Review • Journal
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    FANCI (FA Complementation Group I) • PCNA (Proliferating cell nuclear antigen) • FANCD2 (FA Complementation Group D2) • USP1 (Ubiquitin Specific Peptidase 1)
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    irinotecan
    3ms
    Human cytomegalovirus regulates host DNA repair machinery for viral genome integrity. (PubMed, Nucleic Acids Res)
    This work provides mechanistic insight into the long-standing questions of how DNA viruses recruit, modulate and use cellular DDR pathways. It also puts forth CMV as a model system for further defining these pathways in human cells.
    Journal
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    FANCI (FA Complementation Group I) • PCNA (Proliferating cell nuclear antigen) • FANCD2 (FA Complementation Group D2) • USP1 (Ubiquitin Specific Peptidase 1)
    3ms
    The SMC5/SMC6 complex is critical for resolving R-loop-induced transcription-replication conflicts. (PubMed, Nucleic Acids Res)
    These studies underscore the role of SMC5/6 in sensing TRCs and define the SMC5/6-BTRR-FANCM-FANCD2 axis as an important player in mitigating TRC-induced genome instability. Our findings also provide therapeutic opportunities for targeting this axis for effective treatment of SETX-deficient tumors.
    Journal
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    FANCM (FA Complementation Group M) • FANCD2 (FA Complementation Group D2)
    3ms
    FANCD2 promotes wound healing through DNMT1. (PubMed, Histochem Cell Biol)
    These findings suggest that FANCD2 affects wound healing through DNMT1. These findings may provide novel therapeutic ideas for clinical treatment of patients with FA with poor wound healing.
    Journal
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    DNMT1 (DNA methyltransferase 1) • FANCD2 (FA Complementation Group D2)