Protein-coding gene in the species Homo sapiens
MGME1 |
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Identifiers |
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Aliases | MGME1, C20orf72, DDK1, MTDPS11, bA504H3.4, mitochondrial genome maintenance exonuclease 1 |
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External IDs | OMIM: 615076; MGI: 1921778; HomoloGene: 12573; GeneCards: MGME1; OMA:MGME1 - orthologs |
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Gene location (Human) |
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| Chr. | Chromosome 20 (human)[1] |
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| Band | 20p11.23 | Start | 17,969,018 bp[1] |
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End | 17,991,122 bp[1] |
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Gene location (Mouse) |
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| Chr. | Chromosome 2 (mouse)[2] |
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| Band | 2|2 G1 | Start | 144,112,583 bp[2] |
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End | 144,123,147 bp[2] |
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RNA expression pattern |
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Bgee | Human | Mouse (ortholog) |
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Top expressed in | - skin of arm
- myocardium of left ventricle
- cardiac muscle tissue of right atrium
- ventricular zone
- human penis
- amniotic fluid
- skin of thigh
- gingival epithelium
- trabecular bone
- deltoid muscle
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| Top expressed in | - interventricular septum
- gastrula
- epiblast
- embryo
- morula
- right kidney
- blastocyst
- proximal tubule
- yolk sac
- muscle of thigh
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| More reference expression data |
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BioGPS | |
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Gene ontology |
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Molecular function | - nuclease activity
- single-stranded DNA exodeoxyribonuclease activity
- exonuclease activity
- hydrolase activity
| Cellular component | | Biological process | - mitochondrial DNA replication
- mitochondrial DNA repair
- mitochondrial genome maintenance
- DNA repair
- nucleic acid phosphodiester bond hydrolysis
- cellular response to DNA damage stimulus
| Sources:Amigo / QuickGO |
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Orthologs |
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Species | Human | Mouse |
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Entrez | | |
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Ensembl | | |
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UniProt | | |
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RefSeq (mRNA) | |
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NM_001310338 NM_001310339 NM_052865 NM_001363738 |
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NM_001289630 NM_001289631 NM_028984 NM_001355688 |
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RefSeq (protein) | |
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NP_001297267 NP_001297268 NP_443097 NP_001350667 |
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NP_001276559 NP_001276560 NP_083260 NP_001342617 |
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Location (UCSC) | Chr 20: 17.97 – 17.99 Mb | Chr 2: 144.11 – 144.12 Mb |
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PubMed search | [3] | [4] |
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Wikidata |
View/Edit Human | View/Edit Mouse |
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Mitochondrial genome maintenance exonuclease 1, abbreviated as MGME1, is an enzyme that in humans is encoded by the MGME1 gene.[5][6] MGME1 is a 344 amino acids long protein belonging to the PD-(D/E)XK family of nucleases.[5][6] It localizes to mitochondria where it is important for maintenance of the mitochondrial genome. Loss of function mutations in MGME1 lead to defects in mitochondrial DNA, including mitochondrial DNA depletion, duplications, deletions and increased replication intermediates.[6][5][7] Also, there is an accumulation of 7S DNA, a short single stranded linear DNA strand. MGME1 deficiency in humans leads to multisystemic mitochondrial disease.[5]
Function
The activity of MGME1 has been studied using the purified protein in cell-free in vitro assays. Together these studies suggest that MGME1 functions to remove single stranded nucleotide flaps that arise during mitochondrial DNA replication and/or DNA repair. MGME1 has a strong preference for cutting single stranded DNA, with weak activity on duplex DNA, and no activity on RNA.[5][6] It acts as an endo-/exonuclease, requiring a free 5´or 3´ end for cleavage.[5][6] MGME1 can cut 5´ flap substrates that mimic primer/repair intermediates.[5][8] Moreover, MGME1 removes single stranded 5´-flaps in reconstituted mitochondrial DNA replication assays where it is required to enable ligation of the newly synthesized strand.[8]
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000125871 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000027424 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ a b c d e f g Kornblum C, Nicholls TJ, Haack TB, Schöler S, Peeva V, Danhauser K, et al. (February 2013). "Loss-of-function mutations in MGME1 impair mtDNA replication and cause multisystemic mitochondrial disease". Nature Genetics. 45 (2): 214–9. doi:10.1038/ng.2501. PMC 3678843. PMID 23313956.
- ^ a b c d e Szczesny RJ, Hejnowicz MS, Steczkiewicz K, Muszewska A, Borowski LS, Ginalski K, Dziembowski A (March 2013). "Identification of a novel human mitochondrial endo-/exonuclease Ddk1/c20orf72 necessary for maintenance of proper 7S DNA levels". Nucleic Acids Research. 41 (5): 3144–61. doi:10.1093/nar/gkt029. PMC 3597694. PMID 23358826.
- ^ Nicholls TJ, Zsurka G, Peeva V, Schöler S, Szczesny RJ, Cysewski D, et al. (December 2014). "Linear mtDNA fragments and unusual mtDNA rearrangements associated with pathological deficiency of MGME1 exonuclease". Human Molecular Genetics. 23 (23): 6147–62. doi:10.1093/hmg/ddu336. PMC 4222359. PMID 24986917.
- ^ a b Uhler JP, Thörn C, Nicholls TJ, Matic S, Milenkovic D, Gustafsson CM, Falkenberg M (July 2016). "MGME1 processes flaps into ligatable nicks in concert with DNA polymerase γ during mtDNA replication". Nucleic Acids Research. 44 (12): 5861–71. doi:10.1093/nar/gkw468. PMC 4937333. PMID 27220468.