MGME1 cleaves 5' DNA flap from nascent mitochondrial DNA

Stable Identifier
R-HSA-9914870
Type
Reaction [transition]
Species
Homo sapiens
Compartment
mitochondrial matrix
ReviewStatus
5/5
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MGME1 cleaves 5' DNA flap from nascent mitochondrial DNA
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MGME1, a nuclease that cleaves single-stranded DNA, cleaves 5' flap structures (Kornblum et al. 2013, Yang et al. 2018, Mao et al. 2024)created by the strand-displacement synthesis activity of POLG:POLG2 and allows subsequent ligation of the DNA ends in vitro (Uhler et al. 2016). Loss of MGME1 leads to altered 5′ ends of DNA species in the non-coding region of mitochondrial DNA, revealing the involvement of MGME1 in the 5′-end processing of the H strand (Nicholls et al. 2014). Mice in which Mgme1 is knocked out accumulate 11kb linear mitochondrial DNA that appears to reflect a defect in DNA synthesis termination and ligation (Matic et al. 2018, Milenkovic et al. 2022).
Literature References
PubMed ID Title Journal Year
30247721 Structural insights into DNA degradation by human mitochondrial nuclease MGME1

Yang, C, Wu, R, Liu, H, Chen, Y, Gao, Y, Chen, X, Li, Y, Ma, J, Li, J, Gan, J

Nucleic Acids Res 2018
27220468 MGME1 processes flaps into ligatable nicks in concert with DNA polymerase γ during mtDNA replication

Uhler, JP, Thörn, C, Nicholls, TJ, Matic, S, Milenkovic, D, Gustafsson, CM, Falkenberg, M

Nucleic Acids Res 2016
24986917 Linear mtDNA fragments and unusual mtDNA rearrangements associated with pathological deficiency of MGME1 exonuclease

Nicholls, TJ, Zsurka, G, Peeva, V, Schöler, S, Szczesny, RJ, Cysewski, D, Reyes, A, Kornblum, C, Sciacco, M, Moggio, M, Dziembowski, A, Kunz, WS, Minczuk, M

Hum Mol Genet 2014
38471810 Structural basis of how MGME1 processes DNA 5' ends to maintain mitochondrial genome integrity

Mao, EYC, Yen, HY, Wu, CC

Nucleic Acids Res 2024
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Catalyst Activity

5'-flap endonuclease activity of MGME1 [mitochondrial matrix]

Physical Entity
MGME1 [mitochondrial matrix] (Homo sapiens)
Activity
5'-flap endonuclease activity (GO:0017108)
Authored
May, B  (2024-06-24)
Reviewed
Wu, CC  (2024-10-27)
Created
May, B  (2024-06-30)
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