Mitochondrial genome maintenance exonuclease 1 (MGME1)

Mitochondrial genome maintenance exonuclease 1 (MGME1) is a metal-dependent, PD-(D/E)XK family single-stranded DNA exonuclease that localizes to mitochondria, where it is essential for the maintenance and replication of mitochondrial DNA (mtDNA)[1][3][8]. MGME1 preferentially cleaves single-stranded DNA flaps, performing both exonucleolytic (from a free 5′ or 3′ end) and endonucleolytic cleavage, but does not act on RNA[2][4][8]. Its activity is critical in processing primer/repair intermediates that arise during mtDNA replication, enabling the ligation of newly synthesized DNA strands and regulating the level of replication intermediates such as 7S DNA[1][2][7][8]. Loss-of-function mutations result in decreased mtDNA copy number, rearrangements, and accumulation of 7S DNA, causing multisystemic mitochondrial diseases in humans and tissue-dependent mtDNA defects in model organisms[1][3][7]. MGME1's function is tightly regulated and functionally associates with the DNA replicase Polγ[2][4]. Relevant details have been standardized per conventions provided, with disease and safety implications noted from functional and genetic studies. No approved drugs target MGME1 directly, and no drug mechanisms of action could be found in this context.

Other names

MGME1C20orf72DDK1MTDPS11bA504H3.4