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GENE:

SLX4 (SLX4 Structure-Specific Endonuclease Subunit)

News alerts, weekly reports and conference planners

11d

ZEB1 Promotes Alternate Lengthening of Telomeres at Multiple Levels. (PubMed, Cancers (Basel))

These findings suggest a novel role for ZEB1 in promoting ALT both transcriptionally and post-transcriptionally at multiple levels.

11 days ago

Journal

POLD1 (DNA Polymerase Delta 1) • WRN (WRN RecQ Like Helicase) • ESRP1 (Epithelial Splicing Regulatory Protein 1) • ZEB1 (Zinc Finger E-box Binding Homeobox 1) • RPA3 (Replication Protein A3) • SLX4 (SLX4 Structure-Specific Endonuclease Subunit)

Secoemestrin C exerts rapid and prominent anti-breast cancer effect in triple-negative breast cancer by inducing SLX4 and YAP degradation. (PubMed, Acta Pharmacol Sin)

Specifically, Sec C initiated MDA-MB-231 cells to yield ROS that induced SLX4 ubiquitination and degradation, leading to mtDNA damage and exacerbated mitophagy and promoted YAP degradation bypassing YAP-driven DNA repair pathways. This study not only demonstrates that Sec C is a rapid and prominent anti-breast cancer drug for TNBC, but also reveals SLX4 as a novel mtDNA stabilizer supporting breast cancer progression, positioning it as both a prognostic biomarker and therapeutic target.

1 month ago

Journal

SLX4 (SLX4 Structure-Specific Endonuclease Subunit)

2ms

Tumor of Follicular Infundibulum Is Molecularly Distinct From Basal Cell Carcinoma. (PubMed, Am J Dermatopathol)

Overall, the histomorphologic, clinical, and molecular features of TFI support its classification as a distinct and benign entity from BCC. In addition, the presence of recurrent SLX4 alterations suggests that TFI are likely not reactive but rather may represent a true neoplasm.

2 months ago

Journal

TP53 (Tumor protein P53) • SLX4 (SLX4 Structure-Specific Endonuclease Subunit)

TP53 mutation

2ms

Ginsenoside Rh2 Suppresses the Fanconi Anemia Pathway by Inhibiting NF-κB-Mediated FANCL Transcription in Bladder Cancer. (PubMed, Dose Response)

Ginsenoside Rh2 suppresses NF-κB signaling to transcriptionally downregulate FANCL, thereby impairing FA pathway-mediated DNA repair and enhancing cisplatin cytotoxicity in bladder cancer. These findings highlight Rh2 as a potential combinatorial agent to overcome platinum resistance.

2 months ago

Journal

FANCL (FA Complementation Group L) • ERCC4 (ERCC Excision Repair 4, Endonuclease Catalytic Subunit) • FANCI (FA Complementation Group I) • PCNA (Proliferating cell nuclear antigen) • FANCD2 (FA Complementation Group D2) • SLX4 (SLX4 Structure-Specific Endonuclease Subunit)

cisplatin

2ms

The BRCA1- RAD51 Axis Regulates SCAI/REV3 Dependent Replication Fork Maintenance. (PubMed, bioRxiv)

We posit that SCAI/REV3 may be required to replicate through and rescue stalled replication forks at fragile genomic regions. Failure to do so leads to increased DNA breakage and genomic instability.

2 months ago

Journal

BRCA1 (Breast cancer 1, early onset) • RAD51 (RAD51 Homolog A) • RIF1 (Replication Timing Regulatory Factor 1) • TP53BP1 (Tumor Protein P53 Binding Protein 1) • SLX4 (SLX4 Structure-Specific Endonuclease Subunit)

3ms

TSN Disrupts Fanconi Anemia Pathway Activation Through JAK/STAT1-Mediated Transcriptional Repression of FA Core Subunits in Bladder Cancer. (PubMed, Dose Response)

TSN selectively sensitized bladder cancer cells to UVC-induced cytotoxicity (IC50 decreased 35%, P = 0.026, n = 3), without affecting the viability of human urothelial cell SV-HUC-1 cells or lung adenocarcinoma A549 cells (both P > 0.05, n = 3). TSN inhibits FA DNA repair signaling in bladder cancer by suppressing JAK/STAT1-mediated FA core gene transcription, supporting its potential as a combinatorial agent to overcome cisplatin resistance.

3 months ago

Journal

FANCA (FA Complementation Group A) • FANCF (FA complementation group F) • FANCI (FA Complementation Group I) • FANCM (FA Complementation Group M) • STAT1 (Signal Transducer And Activator Of Transcription 1) • FANCD2 (FA Complementation Group D2) • FANCC (FA Complementation Group C) • SLX4 (SLX4 Structure-Specific Endonuclease Subunit)

cisplatin

3ms

The CIP2A-TOPBP1 axis facilitates mitotic DNA repair via MiDAS and MMEJ. (PubMed, Nat Commun)

The simultaneous functional disruption of both MiDAS and MMEJ pathways upon CIP2A loss provides rationale for the synthetic lethality observed in BRCA1 or 2-deficient cells. These findings position the CIP2A-TOPBP1 axis as a central regulatory hub for mitotic DNA repair, highlighting therapeutic opportunities in tumours characterised by HR deficiency or elevated replication stress.

3 months ago

Journal

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CIP2A (Cellular Inhibitor Of PP2A) • CDK1 (Cyclin-dependent kinase 1) • SLX4 (SLX4 Structure-Specific Endonuclease Subunit)

3ms

Piperine Targets the FANCL/UBE2T Complex to Inhibit the FA Pathway and Sensitize Bladder Cancer to Cisplatin. (PubMed, Dose Response)

Our findings uncover piperine as a natural compound that allosterically inhibits UBE2T activity within the FA pathway, thereby impairing ID2 monoubiquitination and enhancing cisplatin sensitivity in bladder cancer. This study highlights the therapeutic potential of piperine and provides a rationale for targeting the FA repair axis to overcome platinum resistance.

3 months ago

Journal

cisplatin

5ms

RNF4 and USP7 coordinate spatial regulation of SLX4 stability within the PML nuclear bodies. (PubMed, Nucleic Acids Res)

One key regulator of nuclease activity is the scaffold protein SLX4, which plays important roles in repairing DNA damage induced by mitomycin C (MMC) and camptothecin (CPT) as well as in the resolution of stalled replication forks...These findings suggest that SLX4 and its associate nucleases are confined within PML NBs and that the optimal protein level of SLX4 is maintained by the coordinated activities of RNF4 and USP7. Our findings provide insight into how cells effectively control the potentially harmful activities of nucleases in the absence of DNA damage by a spatial regulatory mechanism.

5 months ago

Journal

MUS81 (MUS81 Structure-Specific Endonuclease Subunit) • SLX4 (SLX4 Structure-Specific Endonuclease Subunit) • USP7 (Ubiquitin Specific Peptidase 7)

mitomycin

5ms

Genetic Variants Associated with Breast Cancer Are Detected by Whole-Exome Sequencing in Vietnamese Patients. (PubMed, Diagnostics (Basel))

This is the first WES study to identify BC-associated genetic variants in Vietnamese patients, providing a comprehensive database of BC susceptibility gene variants. We suggest using WES as a tool to identify genetic variants in BC patients for risk prediction and treatment guidance.

5 months ago

Journal

ER (Estrogen receptor) • TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • FGFR2 (Fibroblast growth factor receptor 2) • NF1 (Neurofibromin 1) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • PMS2 (PMS1 protein homolog 2) • MSH3 (MutS Homolog 3) • BARD1 (BRCA1 Associated RING Domain 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • CASP8 (Caspase 8) • WRN (WRN RecQ Like Helicase) • CHD8 (Chromodomain Helicase DNA Binding Protein 8) • RECQL (RecQ Like Helicase) • KLLN (Killin P53 Regulated DNA Replication Inhibitor) • LZTR1 (Leucine Zipper Like Transcription Regulator 1) • RB1CC1 (RB1 Inducible Coiled-Coil 1) • SLX4 (SLX4 Structure-Specific Endonuclease Subunit) • XRCC3 (X-Ray Repair Cross Complementing 3) • ACVR1B (Activin A Receptor Type 1B)

6ms

Exploring Molecular Characteristics and Therapeutic Strategies for Primary Sinonasal Mucosal Melanoma with Distant Metastasis. (PubMed, Lab Invest)

These exploratory findings suggest that SLX4 mutation may serve as a potential prognostic biomarker and that CDK4 inhibitors could represent promising therapeutic options for SNMM-M. However, given the limited sample size, further validation in larger studies is essential to confirm these findings.

6 months ago

Journal • PD(L)-1 Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1) • HRD (Homologous Recombination Deficiency) • SLX4 (SLX4 Structure-Specific Endonuclease Subunit)

PD-L1 expression

6ms

Heterozygous Germline Fanconi Anemia-Related Gene Mutations Increase Susceptibility to Germ Cell Tumors. (PubMed, JCO Precis Oncol)

These results elucidate the contribution of FA-related germline variants to GCT pathogenesis and advance our understanding of the genetic determinants influencing GCT relative risk. This research provides a basis for developing more effective screening strategies, personalized treatment approaches, and improved patient management strategies for GCTs.

6 months ago

Journal • BRCA Biomarker

BRCA2 (Breast cancer 2, early onset) • FANCA (FA Complementation Group A) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • SLX4 (SLX4 Structure-Specific Endonuclease Subunit)