EME1 (N_term)
- Known as:
- EME1 (N_term)
- Catalog number:
- AP13292PU-N
- Product Quantity:
- 0.1 mg
- Category:
- -
- Supplier:
- ACR
- Gene target:
- EME1 (N_term)
Related genes to: EME1 (N_term)
- Gene:
- EME1 NIH gene
- Name:
- essential meiotic structure-specific endonuclease 1
- Previous symbol:
- -
- Synonyms:
- FLJ31364, MMS4L, SLX2A
- Chromosome:
- 17q21.33
- Locus Type:
- gene with protein product
- Date approved:
- 2004-01-27
- Date modifiied:
- 2015-02-24
Related products to: EME1 (N_term)
Related articles to: EME1 (N_term)
- The synthetic lethal interaction between poly(ADP-ribose) polymerase (PARP) inhibition and homologous recombination (HR)-deficiency, particularly in BRCA1/2-mutant tumors, has emerged as an effective strategy for cancer therapy. GEN1, a structure-selective endonuclease that resolves Holliday junctions (HJs) during HR, represents an attractive antitumor target. However, effective small-molecule GEN1 inhibitors have yet to be reported. Here, we established a fluorescence resonance energy transfer (FRET)-based high-throughput screening platform and identified the natural flavonoid scutellarin (SCU) as a specific inhibitor of human GEN1. SCU selectively inhibited GEN1 endonuclease activity against both 5'-flap and HJ DNA substrates, with no effect on other tested structure-selective endonucleases, such as SLX1-SLX4 and MUS81-EME1. Mechanistic studies showed that SCU does not disrupt GEN1-DNA binding but instead binds to the catalytic center of GEN1, thereby inhibiting its endonuclease activity. In HCT116 cells, SCU acted in synergy with the PARP inhibitor olaparib to markedly impair DNA double-strand break (DSB) repair, increase γH2AX accumulation, induce G2/M cell cycle arrest, and suppress cell migration. Notably, the SCU/olaparib combination produced robust synthetic lethality in both HCT116 and HeLa cells, resulting in substantial inhibition of cell viability and colony formation. Our study identifies SCU as a novel selective GEN1 inhibitor, and suggests a new therapeutic strategy that combines GEN1 inhibitors with PARP inhibitors for cancer treatment. - Source: PubMed
Publication date: 2026/08/18
Zhan BinbinZhong YichenChen XueningDai YijunDu LiyangLin ZhonghuiLi Zuoan - To investigate the genetic architecture of male genital lichen sclerosus (MGLSc) and to identify potential susceptibility loci, candidate genes, and biological pathways associated with disease pathogenesis by integrating genomic structural equation modeling (Genomic-SEM) with multi-omics analyses and experimental validation. - Source: PubMed
Publication date: 2026/07/16
Chen JianbaiZhang ZhimingFu QiangHou HaozhongXu GongquanLi ZhenyuLu ZhiguoQiu JianxinWu KeGao XiaopingZhang GengYang LongfeiSong RundongZhang Wei - Cervical cancer is mainly driven by persistent infection with high-risk human papillomaviruses (HPV), particularly HPV16 and HPV18. Despite advances in cytology, HPV-DNA testing and vaccination, challenges remain in the triage of HPV-positive individuals, prognostic stratification and prediction of treatment response. Non-coding RNAs (ncRNAs), including microRNAs, long non-coding RNAs and circular RNAs, together with host genetic factors influencing ncRNA expression and emerging lncRNA-encoded peptides, are increasingly recognized as regulators of HPV-associated carcinogenesis. This review summarizes their biological and potential clinical relevance. A structured literature search was conducted in PubMed and Scopus. Eligible studies included experimental, clinical, observational, genomic and translational investigations on ncRNA dysregulation, circulating or exosomal ncRNAs, treatment-response signatures, host genetic variation and lncRNA-encoded peptides in HPV-associated cervical precancer and cancer. HPV oncoproteins can reshape host ncRNA networks through transcriptional and epigenetic mechanisms. Several miRNAs, lncRNAs and circRNAs are involved in cell-cycle control, apoptosis, senescence, epithelial-mesenchymal transition, immune regulation, DNA repair and treatment resistance. Circulating, exosomal and urinary ncRNA signatures have shown diagnostic or prognostic potential in exploratory cohorts. Specific lncRNAs, including ENSG00000267838/lnc-LENG9-5 and lncRNA-EME1, have been associated with chemoradiotherapy response and radioresistance. The lncRNA-encoded peptide TUBORF represents a novel preclinical therapeutic candidate, while genetic variation may further modulate lncRNA function in HPV-related cervical cancer. ncRNAs are promising candidates for risk stratification, non-invasive diagnosis, treatment-response prediction and therapeutic development in HPV-associated cervical disease. However, evidence remains exploratory, requiring prospective multicentre validation and standardized workflows before clinical implementation. - Source: PubMed
Publication date: 2026/06/21
Terrinoni MatteoCaputo ValerioPalisciano MicheleMascellino GiuseppeGerli SandroFavilli Alessandro - SLX4 is a scaffold protein pivotal in genome protection mechanisms ranging from homologous recombination and interstrand cross-link (ICL) repair to mechanisms that deal with challenged DNA replication. Many of human SLX4 functions rely on its ability to interact and control the XPF-ERCC1, MUS81-EME1, and SLX1 structure-specific endonucleases. Interaction with MUS81 relies on the conserved SAP domain of SLX4. Since the same domain in yeast Slx4 orthologs does not interact with Mus81, we investigated whether human SLX4 SAP might have retained some ancestral MUS81-independent functions. We show that human SLX4 SAP binds DNA with a preference for branched structures such as Holliday junctions. We further discovered that phosphorylation of SLX4 SAP by CDK1, which promotes interaction with MUS81, inhibits DNA binding. We identified separation of function mutants that impair either DNA or MUS81 binding. Binding to MUS81 is required in response to ICL-inducing agents, methyl methanesulfonate (MMS), TOP1, and PARP inhibition. Instead, DNA binding is required in response to ICL-inducing agents and MMS but not after TOP1 or PARP inhibition. Our work indicates that phosphorylation by CDK1 acts as a regulatory switch between DNA binding and MUS81-dependent functions of SLX4, to accommodate specific DNA lesions or secondary structures. - Source: PubMed
Scaglione SarahGaillard Pierre-Henri - Recombinational repair provides an important pathway for the repair of DNA double strand breaks that arise in mitotic and meiotic cells. Homologous pairing and strand exchange leads to the formation of DNA intermediates that are linked by double Holliday junctions, and these need to be resolved prior to chromosome segregation and cell division. In mitotic cells, resolution occurs by either of two distinct pathways (i) Nucleolytic cleavage by GEN1 or SLX1-SLX4-MUS81-EME1-XPF-ERCC1 (SMX complex), or (ii) dissolution mediated by BLM-TopoIIIα-RMI1-RMI2 (BTRR complex). To facilitate the biochemical analysis of these pathways, we previously developed a novel methodology, involving DNAzyme self-cleavage, to generate 1.8-kb long DNA molecules containing dHJs. This involved the sequential annealing of precursor ssDNAs, which were first individually isolated through multiple rounds of gel purification and ethanol precipitation, but unfortunately the method was laborious and inefficient as considerable DNA losses were incurred at each step. Here, we describe a significantly improved methodology, that increases both the efficiency and yield without impacting the quality of the dHJs produced. The new method is rapid and simple, requiring only basic molecular biology expertise, and results in the formation of dHJs that make ideal substrates for the biochemical analysis of dissolution and resolution reaction in vitro. - Source: PubMed
Publication date: 2026/03/25
Shah Punatar RajveeHo Han NWest Stephen C