EME1

Last update 08 May 2025

Basic Info

Synonyms

Crossover junction endonuclease EME1, EME1, essential meiotic structure-specific endonuclease 1

+ [6]

Introduction

Interacts with MUS81 to form a DNA structure-specific endonuclease with substrate preference for branched DNA structures with a 5'-end at the branch nick. Typical substrates include 3'-flap structures, replication forks and nicked Holliday junctions. May be required in mitosis for the processing of stalled or collapsed replication forks.

100 Clinical Results associated with EME1

100 Translational Medicine associated with EME1

0 Patents (Medical) associated with EME1

238

Literatures (Medical) associated with EME1

03 May 2025·British Journal of Cancer

SETD1A-dependent EME1 transcription drives PARPi sensitivity in HR deficient tumour cells

Article

Author: Selemane, Richad ; Bayley, Rachel ; Sweatman, Ellie ; Higgs, Martin R

AbstractBackgroundCells deficient in DNA repair factors breast cancer susceptibility 1/2 (BRCA1/2) or ataxia-telangiectasia mutated (ATM) are sensitive to poly-ADP ribose polymerase (PARP) inhibitors. Building on our previous findings, we asked how the lysine methyltransferase SETD1A contributed to PARP inhibitor-mediated cell death in these contexts and determined the mechanisms responsible.MethodsWe used cervical, breast, lung and ovarian cancer cells bearing mutations in BRCA1 or ATM and depleted SETD1A using siRNA or CRISPR/Cas9. We assessed the effects of the PARPi Olaparib on cell viability, homologous recombination, and DNA repair. We assessed underlying transcriptional perturbations using RNAseq. We used The Cancer Genomics Atlas (TCGA) and DepMap to investigate patient survival and cancer cell characteristics.ResultsLoss of SETD1A from both BRCA1-deficient and ATM-deficient cancer cells was associated with resistance to Olaparib, explained by partial restoration of homologous recombination. Mechanistically, SETD1A-dependent transcription of the crossover junction endonuclease EME1 correlated with sensitivity to Olaparib in these cells. Accordingly, when SETD1A or EME1 was lost, BRCA1 or ATM-mutated cells became resistant to Olaparib, and homologous recombination was partially restored.ConclusionsLoss of SETD1A or EME1 drives cellular resistance to Olaparib in certain genetic contexts and may help explain why patients develop resistance to PARP inhibitors in the clinic.

01 Mar 2025·Trends in Biotechnology

Inducible regulating homologous recombination enables precise genome editing in Pichia pastoris without perturbing cellular fitness

Article

Author: Cai, Peng ; Yao, Lun ; Zhou, Yongjin J ; Li, Yunxia ; Bai, Fan ; Shen, Yiwei

The methylotrophic yeast Pichia pastoris (also known as Komagataella pastoris) is an ideal host for producing proteins and natural products. Enhancing homologous recombination (HR) is helpful for improving the precision of genome editing, but results in stress to cellular fitness and is harmful for industrial applications. To overcome these challenges, we developed a tetracycline repressor protein (TetR)/tetO2 inducible system to dynamically regulate the HR-related gene RAD52 in P. pastoris. This approach significantly improved the positivity rate of single gene deletion to 81%. Furthermore, inducible overexpression of endogenous MUS81-MMS4 resulted in high-efficiency (81%) genome assembly of multiple genes. This inducible system had no adverse effect on cell growth in different media and resulted in greater fatty alcohol production from methanol compared with a strain constitutively overexpressing HR-related genes. We anticipate that this inducible regulation is applicable for enhancing HR for precise genome editing in P. pastoris and other non-conventional microbes without compromising cellular fitness.

17 Feb 2025·Journal of Clinical Investigation

CRISPR/Cas9 screens identify LIG1 as a sensitizer of PARP inhibitors in castration-resistant prostate cancer

Article

Author: Gioia, Ubaldo ; Demichelis, Francesca ; Mateo, Joaquin ; d'Adda di Fagagna, Fabrizio ; Prandi, Davide ; Casaramona, Arnau S ; Lorenzin, Francesca ; Santer, Frédéric R ; Fracassi, Giulia ; Orlando, Francesco ; Cantore, Thomas ; Klocker, Helmut ; D'Amato, Giacomo

PARP inhibitors (PARPi) have received regulatory approval for the treatment of several tumors, including prostate cancer (PCa), and demonstrate remarkable results in the treatment of castration-resistant prostate cancer (CRPC) patients characterized by defects in homologous recombination repair (HRR) genes. Preclinical studies showed that DNA repair genes (DRG) other than HRR genes may have therapeutic value in the context of PARPi. To this end, we performed multiple CRISPR/Cas9 screens in PCa cell lines using a custom sgRNA library targeting DRG combined with PARPi treatment. We identified DNA ligase 1 (LIG1), essential meiotic structure-specific endonuclease 1 (EME1), and Fanconi anemia core complex associated protein 24 (FAAP24) losses as PARPi sensitizers and assessed their frequencies from 3% to 6% among CRPC patients. We showed that concomitant inactivation of LIG1 and PARP induced replication stress and DNA double-strand breaks, ultimately leading to apoptosis. This synthetic lethality (SL) is conserved across multiple tumor types (e.g., lung, breast, and colorectal), and its applicability might be extended to LIG1-functional tumors through a pharmacological combinatorial approach. Importantly, the sensitivity of LIG1-deficient cells to PARPi was confirmed in vivo. Altogether, our results argue for the relevance of determining the status of LIG1 and potentially other non-HRR DRG for CRPC patient stratification and provide evidence to expand their therapeutic options.

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EME1

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