MGME1

Last update 08 May 2025

Basic Info

Synonyms

bA504H3.4, C20orf72, DDK1

+ [2]

Introduction

Metal-dependent single-stranded DNA (ssDNA) exonuclease involved in mitochondrial genome maintenance. Has preference for 5'-3' exonuclease activity but is also capable of endoduclease activity on linear substrates. Necessary for maintenance of proper 7S DNA levels. Probably involved in mitochondrial DNA (mtDNA) repair, possibly via the processing of displaced DNA containing Okazaki fragments during RNA-primed DNA synthesis on the lagging strand or via processing of DNA flaps during long-patch base excision repair. Specifically binds 5-hydroxymethylcytosine (5hmC)-containing DNA in stem cells.

100 Clinical Results associated with MGME1

100 Translational Medicine associated with MGME1

0 Patents (Medical) associated with MGME1

Literatures (Medical) associated with MGME1

01 Apr 2025·Biochemical and Biophysical Research Communications

Unspliced XBP1 enhences metabolic reprogramming in colorectal cancer cells by interfering with the mitochondrial localization of MGME1

Article

Author: Huang, Can ; Zhang, Jiandong ; Wu, Mingyue ; Zhang, Suyang ; Yu, Fei ; Wan, Yuting

Tumor cells undergo metabolic reprogramming, which makes them tend to utilize anaerobic glycolysis rather than oxidation to rapidly produce energy and intermediate products required for proliferation. In this process, mitochondria inevitably undergo corresponding alterations; however, the specific alterations in mitochondria across different cancer types and the mechanisms governing these changes remain poorly understood. This study demonstrated that unspliced X-box binding protein 1 (XBP1-u) inhibits the translocation of mitochondrial genome maintenance exonuclease 1 (MGME1) into mitochondria by binding to the mitochondrial targeting sequence (MTS) of MGME1. This interaction results in the accumulation of mitochondrial 7sDNA, a reduction in mitochondrial DNA copy number, and a decrease in mitochondrial abundance. Consequently, this shift enhances the production of glycolysis and pentose phosphate pathway intermediates, thereby promoting the proliferation of colorectal cancer (CRC) cells. Our findings elucidated the critical mechanism by which XBP1-u enhances metabolic reprogramming by modulating mitochondrial biogenesis, and uncovered a novel role of MGME1 in the progression of CRC.

27 Feb 2025·Nucleic Acids Research

Mitochondrial exonuclease EXOG supports DNA integrity by the removal of single-stranded DNA flaps

Article

Author: Czub, Jacek ; Dubiel, Andrzej B ; Hossain, Kazi Amirul ; Wyszkowska, Marta ; Karlowicz, Anna ; Szymanski, Michal R

AbstractSingle-stranded DNA (ssDNA) is an important intermediate generated during various cellular DNA transactions, primarily during long-patch base excision repair. When displaced by DNA polymerase during strand displacement DNA synthesis, ssDNA forms 5′ overhangs (flaps) that are either cleaved by DNA nucleases or protected from degradation upon binding of single-stranded DNA-binding proteins (SSB). Several nucleases are involved in the removal of ssDNA flaps in human mitochondria, namely the endonucleases FEN1 and DNA2, as well as the exonuclease MGME1. In this study, we show that another mitochondrial nuclease, EXOG, cleaves DNA flaps in both free and SSB-protected forms. We established that the presence of the Wing domain in EXOG structure provides additional binding site for ssDNA and 5′ flaps irrespective of monovalent salt concentration. Importantly, DNA flap cleavage by EXOG is compatible with the activity of other mitochondrial enzymes involved in DNA replication/repair, e.g. mtSSB, Pol γ, and Lig III, as we were able to reconstitute a multistep reaction of DNA synthesis, flap removal, and nick ligation. Our findings highlight the versatile role of EXOG in maintaining mitochondrial DNA integrity, expanding its DNA processing repertoire to include ssDNA flap removal.

01 Feb 2025·Molecular Biology of the Cell

MRE11-independent effects of Mirin on mitochondrial DNA integrity and cellular immune responses

Article

Author: Goffart, Steffi ; Fragkoulis, Georgios ; Bader, Cyrielle P. J. ; Wanrooij, Sjoerd ; Aasumets, Koit ; Pohjoismäki, Jaakko L.O. ; Hangas, Anu ; Wanrooij, Paulina H. ; Erdinc, Direnis

Mirin, a chemical inhibitor of MRE11, has been recently reported to suppress immune response triggered by mitochondrial DNA (mtDNA) breakage and release during replication stalling. We show that while Mirin reduces mitochondrial replication fork breakage in mitochondrial 3´-exonuclease MGME1 deficient cells, this effect occurs independently of MRE11. We also discovered that Mirin directly inhibits cellular immune responses, as shown by its suppression of STAT1 phosphorylation in Poly (I:C)-treated cells. Furthermore, Mirin also altered mtDNA supercoiling and accumulation of hemicatenated replication termination intermediates—hallmarks of topoisomerase dysfunction—while mitigating topological changes induced by the overexpression of mitochondrial TOP3A, including TOP3A-dependent strand breakage at the noncoding region of mtDNA. Although Mirin does not seem to inhibit TOP3A activity in vitro, our findings demonstrate its MRE11-independent effects in cells and give insight into the mechanisms of the maintenance of mtDNA integrity.

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MGME1

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