Reactome | EXOG cleaves RNA dinucleotide from nascent mitochondrial DNA

EXOG cleaves RNA dinucleotide from nascent mitochondrial DNA

Stable Identifier

R-HSA-9915442

Type

Reaction [transition]

Species

Homo sapiens

Compartment

mitochondrial matrix

ReviewStatus

5/5

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EXOG cleaves RNA dinucleotide from nascent mitochondrial DNA

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The RNA primers that initiate the synthesis of mitochondrial DNA are removed by RNASEH1, which cleaves and removes all but two ribonucleotides, and a second nuclease, which removes the remaining two ribonucleotides (Al-Behadili et al. 2018). Neither the MGME1 nor DNA2 nucleases catalyze the removal of the diribonucleotide (Al-Behadili et al. 2018). In vitro, the mitochondrial nuclease EXOG cleaves the diribonucleotide from DNA 5′ end and provides ligatable DNA ends for LIG3 (Cymerman et al. 2008, Wu et al. 2019, Karlowicz et al. 2022). EXOG interacts with RNASEH1 both in vitro and in cellulo (Karlowicz et al. 2022). Depletion of EXOG by RNAi in human cells causes accumulation of single-strand breaks (Tann et al. 2011), however, loss of EXOG in rat cardiomyocytes was not observed to cause loss of mitochondrial DNA integrity (Tigchelaar et al. 2015).

Literature References

PubMed ID	Title	Journal	Year
35819194	In vitro reconstitution reveals a key role of human mitochondrial EXOG in RNA primer processing Karlowicz, A, Dubiel, AB, Czerwinska, J, Bledea, A, Purzycki, P, Grzelewska, M, McAuley, RJ, Szczesny, RJ, Brzuska, G, Krol, E, Szczesny, B, Szymanski, MR	Nucleic Acids Res	2022
30949702	A unique exonuclease ExoG cleaves between RNA and DNA in mitochondrial DNA replication Wu, CC, Lin, JLJ, Yang-Yen, HF, Yuan, HS	Nucleic Acids Res	2019
18187503	EXOG, a novel paralog of Endonuclease G in higher eukaryotes Cymerman, IA, Chung, I, Beckmann, BM, Bujnicki, JM, Meiss, G	Nucleic Acids Res	2008