The POLγ Y951N patient mutation disrupts the switch between DNA synthesis and proofreading, triggering mitochondrial DNA instability
Josefin M. E. Forslund, Tran V. H. Nguyen, Vimal Parkash, Andreas Berner, Steffi Goffart, Jaakko L. O. Pohjoismäki, Paulina H. Wanrooij, Erik Johansson , and Sjoerd Wanrooij.
Proc. Natl. Acad. Sci. U.S.A. 122 (16) e2417477122,(2025). https://doi.org/10.1073/pnas.2417477122
Activating AMPK improves pathological phenotypes due to mtDNA depletion
Gustavo Carvalho, Tran V. H. Nguyen, Bruno Repolês, Josefin M. E. Forslund, W. M. Ruchitha Rukmal Wijethunga, Farahnaz Ranjbarian, Isabela C. Mendes, Choco Michael Gorospe, Namrata Chaudhari, Micol Falabella, Mara Doimo, Sjoerd Wanrooij, Robert D. S. Pitceathly, Anders Hofer, Paulina H.
The FEBS journal (2025). https://doi.org/10.1111/febs.70006
G4-ligand-conjugated oligonucleotides mediate selective binding and stabilization of individual G4 DNA structures.
Berner A, Das RN, Bhuma N, Golebiewska J, Abrahamsson A, Andréasson M, Chaudhari N, Doimo M, Bose PP, Chand K, Strömberg R, Wanrooij S, Chorell E.
Journal of the American Chemical Society, American Chemical Society (ACS) (2024);146(10):6926-6935. https://pubs.acs.org/doi/10.1021/jacs.3c14408
Exploring the dispersion and electrostatic components in arene-arene interactions between ligands and G4 DNA to develop G4-ligands.
Andreasson M, Donzel M, Abrahamsson A, Berner A, Doimo M, Quiroga A, Eriksson A, Chao YK, Overman J, Pemberton N, Wanrooij S, Chorell E.
J Med Chem. (2024);67(3):2202-2219. https://pubs.acs.org/doi/10.1021/acs.jmedchem.3c02127
Rolling Circle Replication and Bypass of Damaged Nucleotides.
Forslund, J.M.E., Stojkovič, G., Wanrooij, S., Nicholls, T.J., Uhler, J.P., Falkenberg, M. (eds)
Mitochondrial DNA (2023). Methods in Molecular Biology, vol 2615. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-2922-2_15
Enhanced mitochondrial G-quadruplex formation impedes replication fork progression leading to mtDNA loss in human cells.
Doimo M, Chaudhari N, Abrahamsson S, L’Hôte V, Nguyen TVH, Berner A, Ndi M, Abrahamsson A, Das RN, Aasumets K, Goffart S, Pohjoismäki JLO, López MD, Chorell E, Wanrooij S.
Nucleic Acids Research, Oxford University Press (2023), Vol. 51, (14) : 7392-7408. https://academic.oup.com/nar/article/51/14/7392/7205764?login=true
Unravelling the Therapeutic Potential of Antibiotics in Hypoxia in a Breast Cancer MCF-7 Cell Line Model.
Akhunzianov AA, Nesterova AI, Wanrooij S, Filina YV, Rizvanov AA, Miftakhova RR.
Int. J. Mol. Sci. 2023, 24(14), 11540; https://doi.org/10.3390/ijms241411540
Motif WFYY of human PrimPol is crucial to stabilize the incoming 3′-nucleotide during replication fork restart
Calvo, Patricia A; Martínez-Jiménez, María I; Díaz, Marcos; et al.
Nucleic Acids Research, Oxford University Press 2021, Vol. 49, (14) : 8199-8213. https://doi.org/10.1093/nar/gkab634
Human polymerase δ-interacting protein 2 (Poldip2) inhibits the formation of human tau oligomers and fibrils
Kasho, Kazutoshi; Krasauskas, Lukas; Smirnovas, Vytautas; et al.
International Journal of Molecular Sciences, MDPI 2021, Vol. 22, (11). https://doi.org/10.3390/ijms22115768
A unique arginine cluster in PolDIP2 enhances nucleotide binding and DNA synthesis by PrimPol
Kasho, Kazutoshi; Stojkovic, Gorazd; Velázquez-Ruiz, Cristina; et al.
Nucleic Acids Research, Oxford University Press 2021, Vol. 49, (4) : 2179-2191. https://doi.org/10.1093/nar/gkab049
MtDNA replication, maintenance, and nucleoid organization
Doimo, Mara; Pfeiffer, Annika; Wanrooij, Paulina H.; et.al
The Human Mitochondrial Genome: From Basic Biology to Disease, Academic Press 2020 : 3-33. https://doi.org/10.1016/B978-0-12-819656-4.00001-2
Quinazoline ligands induce cancer cell death through selective STAT3 inhibition and G-quadruplex stabilization
Jamroskovic J, Doimo M, Chand K, Obi I, Kumar R, Brännström K, Hedenström M, Nath Das R, Akhunzianov A, Deiana M, Kasho K, Sulis Sato S, Pourbozorgi PL, Mason JE, Medini P, Öhlund D, Wanrooij S*, Chorell E*, Sabouri N*.
J Am Chem Soc (2020). 142 (6) 2876-2888. https://pubmed.ncbi.nlm.nih.gov/31990532/.
*Shared last author.
Photoactivated colibatin probes induce in vitro DNA damage.
Moodle LWK, Hubert M, Zhou X, Albers MF, Lundmark R, Wanrooij S and Hedberg C.
Angewandte Chemie (2019). 58(5):1417-1421. https://pubmed.ncbi.nlm.nih.gov/30506956/
The presence of rNTPs decreases the speed of mitochondrial DNA replication.
Forslund JME, Pfeiffer A, Stojkovič G, Wanrooij PH and Wanrooij S
PLOS Genetics (2018). 14(3):e1007315 https://pubmed.ncbi.nlm.nih.gov/29601571/
Known and unknowns of mammalian mitochondrial DNA maintenance.
Pohjoismäki JLO, Forslund JME, Goffart S, Torregrosa-Muñumer R and Wanrooij S.
BioEssays (2018) 40(9):e1800102. https://pubmed.ncbi.nlm.nih.gov/29999547/
A two-nuclease pathway involving RNase H1 is required for primer removal at OriL.
Al-Behadili A, Uhler JP, Berglund AK, Bradley P, Doimo M, Reyes A, Wanrooij S, Zeviani M and Falkenberg M.Nucleic Acids Res (2018) 46(18):9471-9483. https://pubmed.ncbi.nlm.nih.gov/30102370/
No repair of ribonucleotides misincorporated into yeast mitochondrial DNA.
Wanrooij PH, Engqvist MKM, Forslund JME, Navarrete C, Nilsson AK, Sedman J, Wanrooij S, Clausen AR and Chabes A.
Proc Natl Acad Sci (2017) 114(47):12466-12471 https://pubmed.ncbi.nlm.nih.gov/29109257/
PrimPol is required for replication re-initiation after mitochondrial DNA damage.
Torregrosa-Muñumer R, Forslund J, Goffart S, Stojkovic G, Pfeiffer A, Carvalho G, Al-Furoukh N, Blanco L, Wanrooij S*, Pohjoismäki JLO*.
Proc Natl Acad Sci (2017) 114(43):11398-11403. https://pubmed.ncbi.nlm.nih.gov/29073063/
*shared last author
ATPase-deficient mitochondrial inner membrane protein ATAD3A disturbs mitochondrial dynamics in dominant hereditary spastic paraplegia.
Cooper HM, Yang Y, Ylikallio E, Khairullin R, Woldegebriel R, Kai-Lan L, Euro L, Palin E, Wolf A, Trokovic R, Isohanni P, Kaakkola S, Auranen M, Lönnqvist T, Wanrooij S and Tyynismaa H
Human Mol Genet. (2017) 26(8):1432-1443. https://pubmed.ncbi.nlm.nih.gov/28158749/
Optimization of the expression, purification and polymerase activity reaction conditions of recombinant human PrimPol.
Boldinova EO, Stojkovič G, Khairullin R, Wanrooij S* and Makarova AV*.
PLoS One (2017) 12(9):e0184489. https://pubmed.ncbi.nlm.nih.gov/28902865/
*shared last author.
DNA damage tolerance by eukaryotic DNA polymerase and primase PrimPol
Boldinova EO, Wanrooij PH, Shilkin ES, Wanrooij S+ and Makarova AV+
Int J Mol Sci (2017) 18(7). https://pubmed.ncbi.nlm.nih.gov/28754021/
+ shared last author
Oxidative DNA damage stalls the human mitochondrial replisome.
Stojkovic G, Makarova AV, Wanrooij PH, Forslund J, Burgers PM, Wanrooij S
Sci Rep (2016) 6:28942. https://pubmed.ncbi.nlm.nih.gov/27364318/
ClpX stimulates the mitochondrial unfolded protein response (UPR(mt)) in mammalian cells.
Al-Furoukh N, Ianni A, Nolte H, Hölper S, Krüger M, Wanrooij S, Braun T
Biochim Biophys Acta (2015) 1853: 2580-91. https://pubmed.ncbi.nlm.nih.gov/26142927/
In vivo occupancy of mitochondrial single-stranded DNA binding protein supports the strand displacement mode of DNA replication.
Miralles Fusté J, Shi Y, Wanrooij S, Zhu X, Jemt E, Persson Ö, Sabouri N, Gustafsson CM, Falkenberg M.
PLoS Genetics. (2014) 4;10(12):e1004832. https://pubmed.ncbi.nlm.nih.gov/25474639/
Binding to G-quadruplex RNA activates the mitochondrial GTPase NOA1.
Al-Furoukh N, Goffart S, Szibor M, Wanrooij S and Braun T
Biochim Biophys Acta (2013) 1833(12):2933-2942. https://pubmed.ncbi.nlm.nih.gov/23933583/
Mammalian transcription factor A is a core component of the mitochondrial transcription machinery.
Shi Y, Dierckx A, Wanrooij PH, Wanrooij S, Larsson NG, Wilhelmsson LM, Falkenberg M and Gustafsson CM
Proc Natl Acad Sci USA (2012) 109: 16510-16515. https://pubmed.ncbi.nlm.nih.gov/23012404/
In vivo mutagenesis reveals that OriL is essential for mitochondrial DNA replication.
Wanrooij S, Miralles Fuste J, Stewart JB, Wanrooij PH, Samuelsson T, Larsson NG, Gustafsson CM and Falkenberg M
EMBO Rep (2012) 13: 1130-1137. https://pubmed.ncbi.nlm.nih.gov/23090476/
Sequence-specific stalling of DNA polymerase gamma and the effects of mutations causing progressive ophthalmoplegia.
Atanassova N, Fuste JM, Wanrooij S, Macao B, Goffart S, Bäckström S, Farge G, Khvorostov I, Larsson NG, Spelbrink JN and Spelbrink JN
Hum Mol Genet (2011) 20: 1212-1223. https://pubmed.ncbi.nlm.nih.gov/21228000/
Mitochondrial RNA polymerase is needed for activation of the origin of light-strand DNA replication.
Fuste JM*, Wanrooij S*, Jemt E, Granycome EG, Cluett TJ, Shi Y, Atanassova N, Holt IJ, Gustafsson CM and Falkenberg M
Mol Cell (2010) 37: 67-78. https://pubmed.ncbi.nlm.nih.gov/20129056/
* Co-first author
The human mitochondrial replication fork in health and disease.
Wanrooij S*, Falkenberg M
Biochim Biophys Acta (2010) 1797: 1378-1388. https://pubmed.ncbi.nlm.nih.gov/20417176/
* Corresponding author
Twinkle mutations associated with autosomal dominant progressive external opthalmoplegia lead to impaired helicase function and in vivo mtDNA replication stalling.
Goffart S, Cooper HM, Tyynismaa H, Wanrooij S, Suomalainen A and Spelbrink JN
Hum Mol Genet (2009) 18: 328-40. https://pubmed.ncbi.nlm.nih.gov/18971204/
Human mitochondrial RNA polymerase primes lagging-strand DNA synthesis in vitro.
Wanrooij S, Fuste JM, Farge G, Shi Y, Gustafsson CM and Falkenberg M
Proc Natl Acad Sci USA (2008) 105: 11122-11127. https://pubmed.ncbi.nlm.nih.gov/18685103/
What causes mitochondrial DNA deletions in human cells?
Krishnan KJ, Reeve AK, Samuels DC, Chinnery PF, Blackwood JK, Taylor RW, Wanrooij S, Spelbrink JN, Lightowlers RN and Turnbull DM
Nature Genetics (2008) 40: 275-279. https://pubmed.ncbi.nlm.nih.gov/18305478/
The mitochondrial termination factor mTERF modulates replication pausing in human mitochondrial DNA.
Hyvärinen A, Pojoismäki JLO, Reyes A, Wanrooij S, Yasukawa T, Karhunen P, Spelbrink JN, Holt IJ and Jacobs HT
Nucleic Acids Res (2007) 35: 6458-6474. https://pubmed.ncbi.nlm.nih.gov/17884915/
Expression of catalytic mutants of the mtDNA helicase and polymerase POLG causes distinct replication stalling phenotypes.
Wanrooij S, Goffart S, Pohjoismäki JLO, Yasukawa T and Spelbrink JN
Nucleic Acids Res (2007) 35: 3238-3251 https://pubmed.ncbi.nlm.nih.gov/17452351/
Alterations to the expression level of mitochondrial transcription factor A, TFAM, modify the mode of mitochondrial DNA replication in cultured human cells.
Pohjoismäki JL, Wanrooij S, Hyvärinen AK, Goffart S, Holt IJ, Spelbrink JN and Jacobs HT
Nucleic Acids Res (2006) 34: 5815-5828. https://pubmed.ncbi.nlm.nih.gov/17062618/
Mutant mitochondrial helicase Twinkle causes multiple mtDNA deletions and a late-onset mitochondrial disease in mice.
Tyynismaa H, Mjosund KP, Wanrooij S, Lappalainen I, Ylikallio E, Jalanko A, Spelbrink JN, Paetau A and Suomalainen A
Proc Natl Acad Sci U S A (2005) 102: 17687-17692. https://pubmed.ncbi.nlm.nih.gov/16301523/
Twinkle and POLG defects enhance age-dependent accumulation of mutations in the control region of mtDNA.
Wanrooij S, Luoma P, van Goethem G, van Broeckhoven C, Suomalainen A and Spelbrink JN (2004)
Nucleic Acids Res (2004) 32: 3053-3064. https://pubmed.ncbi.nlm.nih.gov/15181170
Human mitochondrial DNA deletions associated with mutations in the gene encoding Twinkle, a phage T7 gene 4-like protein localized in mitochondria.
Spelbrink JN, Li FY, Tiranti V, Nikali K, Yuan QP, Tariq M, Wanrooij S, Garrido N, Comi G, Morandi L, Santoro L, Toscano A, Fabrizi GM, Croxen R, Beeson D, Poulton J, Suomalainen A, Jacobs HT, Zeviani M and Larsson C
Nature Genetics (2001) 28: 223-231. https://pubmed.ncbi.nlm.nih.gov/11431692/