Reactome | TWNK (PEO1) unwinds double-stranded mitochondrial DNA at the replication fork

TWNK (PEO1) unwinds double-stranded mitochondrial DNA at the replication fork

Stable Identifier

R-HSA-9914438

Type

Reaction [transition]

Species

Homo sapiens

Compartment

mitochondrial matrix

ReviewStatus

5/5

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TWNK (PEO1) unwinds double-stranded mitochondrial DNA at the replication fork

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TWINKLE (TWNK, PEO1) binds DNA as a hexamer encircling the replication origin and employs energy from ATP hydrolysis to unwind double stranded DNA in advance of the mitochondrial DNA polymerase POLgamma (POLG:POLG2) (Korhonen et al. 2004, Jemt et al. 2011, Sen et al. 2012, Khan et al. 2016, Kaur et al. 2020, Kaur et al. 2021). The N-terminal region of TWNK binds DNA and stabilizes oligomerization while the C-terminal region contains ATPase activity and helicase activity (Johnson et al. 2023). TWNK is required for replication of circular DNA models in vitro (Korhonen et al. 2004, Wanrooij et al. 2008) and observation of Twnk knockout cells from mice indicate that TWNK is essential for nascent synthesis of the H strand in the D-loop at H strand origin of replication (OriH) in vivo (Milenkovic et al. 2013).

Literature References

PubMed ID	Title	Journal	Year
18685103	Human mitochondrial RNA polymerase primes lagging-strand DNA synthesis in vitro Wanrooij, S, Fusté, JM, Farge, G, Shi, Y, Gustafsson, CM, Falkenberg, M	Proc Natl Acad Sci U S A	2008
34604445	Using Atomic Force Microscopy to Study the Real Time Dynamics of DNA Unwinding by Mitochondrial Twinkle Helicase Kaur, P, Pan, H, Longley, MJ, Copeland, WC, Wang, H	Bio Protoc	2021
22383523	Human mitochondrial DNA helicase TWINKLE is both an unwinding and annealing helicase Sen, D, Nandakumar, D, Tang, GQ, Patel, SS	J Biol Chem	2012
32213598	Single-molecule level structural dynamics of DNA unwinding by human mitochondrial Twinkle helicase Kaur, P, Longley, MJ, Pan, H, Wang, W, Countryman, P, Wang, H, Copeland, WC	J Biol Chem	2020
15167897	Reconstitution of a minimal mtDNA replisome in vitro Korhonen, JA, Pham, XH, Pellegrini, M, Falkenberg, M	EMBO J	2004
36528058	The N-terminal domain of human mitochondrial helicase Twinkle has DNA-binding activity crucial for supporting processive DNA synthesis by polymerase γ Johnson, LC, Singh, A, Patel, SS	J Biol Chem	2023
21840902	The mitochondrial DNA helicase TWINKLE can assemble on a closed circular template and support initiation of DNA synthesis Jemt, E, Farge, G, Bäckström, S, Holmlund, T, Gustafsson, CM, Falkenberg, M	Nucleic Acids Res	2011
27226550	Biochemical Characterization of the Human Mitochondrial Replicative Twinkle Helicase: SUBSTRATE SPECIFICITY, DNA BRANCH MIGRATION, AND ABILITY TO OVERCOME BLOCKADES TO DNA UNWINDING Khan, I, Crouch, JD, Bharti, SK, Sommers, JA, Carney, SM, Yakubovskaya, E, Garcia-Diaz, M, Trakselis, MA, Brosh, RM	J Biol Chem	2016