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DELMIT SIGNED

Maintaining the Human Mitochondrial Genome

Total Cost €

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EC-Contrib. €

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Partnership

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Project "DELMIT" data sheet

The following table provides information about the project.

Coordinator
GOETEBORGS UNIVERSITET 

Organization address
address: VASAPARKEN
city: GOETEBORG
postcode: 405 30
website: www.gu.se

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Sweden [SE]
 Project website https://falkenberglab.org/
 Total cost 1˙999˙985 €
 EC max contribution 1˙999˙985 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2015-CoG
 Funding Scheme ERC-COG
 Starting year 2016
 Duration (year-month-day) from 2016-11-01   to  2021-10-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    GOETEBORGS UNIVERSITET SE (GOETEBORG) coordinator 1˙999˙985.00

Map

 Project objective

Mitochondria are required to convert food into usable energy forms and every cell contains thousands of them. Unlike most other cellular compartments, mitochondria have their own genomes (mtDNA) that encode for 13 of the about 90 proteins present in the respiratory chain. All proteins necessary for mtDNA replication, as well as transcription and translation of mtDNA-encoded genes, are encoded in the nucleus. Mutations in nuclear-encoded proteins required for mtDNA maintenance is an important cause of neurodegeneration and muscle diseases. The common result of these defects is either mtDNA depletion or accumulation of multiple deletions of mtDNA in postmitotic tissues.

The long-term goal (or vision) of research in my laboratory is to understand in molecular detail how mtDNA is replicated and how this process is regulated in mammalian cells. To this end we use a protein biochemistry approach, which we combine with in vivo verification in cell lines. My group was in 2004 the first to reconstitute mtDNA replication in vitro and we have continued to develop even more elaborate system ever since. In the current application, the major focus is studies of the mitochondrial D-loop region, a triple-stranded structure in the mitochondrial genome. The D-loop functions as a regulatory hub and we will determine how initiation and termination of mtDNA replication is controlled from this region. We will also determine the physical organization of the mtDNA replication machinery at the replication fork and establish how mtDNA deletions, a classical hallmark of human ageing, are formed.

 Publications

year authors and title journal last update
List of publications.
2019 Viktor Posse, Ali Al-Behadili, Jay P. Uhler, Anders R. Clausen, Aurelio Reyes, Massimo Zeviani, Maria Falkenberg, Claes M. Gustafsson
RNase H1 directs origin-specific initiation of DNA replication in human mitochondria
published pages: e1007781, ISSN: 1553-7404, DOI: 10.1371/journal.pgen.1007781
PLOS Genetics 15/1 2019-08-29
2019 Géraldine Farge, Maria Falkenberg
Organization of DNA in Mammalian Mitochondria
published pages: 2770, ISSN: 1422-0067, DOI: 10.3390/ijms20112770
International Journal of Molecular Sciences 20/11 2019-08-29
2018 Stanka Matic, Min Jiang, Thomas J. Nicholls, Jay P. Uhler, Caren Dirksen-Schwanenland, Paola Loguercio Polosa, Marie-Lune Simard, Xinping Li, Ilian Atanassov, Oliver Rackham, Aleksandra Filipovska, James B. Stewart, Maria Falkenberg, Nils-Göran Larsson, Dusanka Milenkovic
Mice lacking the mitochondrial exonuclease MGME1 accumulate mtDNA deletions without developing progeria
published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-018-03552-x
Nature Communications 9/1 2019-08-29
2017 Tim Bergbrede, Emily Hoberg, Nils-Göran Larsson, Maria Falkenberg, Claes M. Gustafsson
An Adaptable High-Throughput Technology Enabling the Identification of Specific Transcription Modulators
published pages: 378-386, ISSN: 2472-5552, DOI: 10.1177/2472555217690326
SLAS DISCOVERY: Advancing Life Sciences R&D 22/4 2019-06-18
2017 Anna-Karin Berglund, Clara Navarrete, Martin K. M. Engqvist, Emily Hoberg, Zsolt Szilagyi, Robert W. Taylor, Claes M. Gustafsson, Maria Falkenberg, Anders R. Clausen
Nucleotide pools dictate the identity and frequency of ribonucleotide incorporation in mitochondrial DNA
published pages: e1006628, ISSN: 1553-7404, DOI: 10.1371/journal.pgen.1006628
PLOS Genetics 13/2 2019-06-18
2018 Thomas J. Nicholls, Cristina A. Nadalutti, Elisa Motori, Ewen W. Sommerville, Gráinne S. Gorman, Swaraj Basu, Emily Hoberg, Doug M. Turnbull, Patrick F. Chinnery, Nils-Göran Larsson, Erik Larsson, Maria Falkenberg, Robert W. Taylor, Jack D. Griffith, Claes M. Gustafsson
Topoisomerase 3α Is Required for Decatenation and Segregation of Human mtDNA
published pages: 9-23.e6, ISSN: 1097-2765, DOI: 10.1016/j.molcel.2017.11.033
Molecular Cell 69/1 2019-06-18
2017 Maria Falkenberg
Mitochondrial DNA replication in mammalian cells: overview of the pathway
published pages: EBC20170100, ISSN: 0071-1365, DOI: 10.1042/EBC20170100
Essays In Biochemistry 2019-06-18
2018 Bradley Peter, Christie L Waddington, Monika Oláhová, Ewen W Sommerville, Sila Hopton, Angela Pyle, Michael Champion, Monica Ohlson, Triinu Siibak, Zofia M A Chrzanowska-Lightowlers, Robert W Taylor, Maria Falkenberg, Robert N Lightowlers
Defective mitochondrial protease LonP1 can cause classical mitochondrial disease
published pages: 1743-1753, ISSN: 0964-6906, DOI: 10.1093/hmg/ddy080
Human Molecular Genetics 27/10 2019-06-18
2017 Amandine Moretton, Frédéric Morel, Bertil Macao, Philippe Lachaume, Layal Ishak, Mathilde Lefebvre, Isabelle Garreau-Balandier, Patrick Vernet, Maria Falkenberg, Géraldine Farge
Selective mitochondrial DNA degradation following double-strand breaks
published pages: e0176795, ISSN: 1932-6203, DOI: 10.1371/journal.pone.0176795
PLOS ONE 12/4 2019-06-18
2017 Triinu Siibak, Paula Clemente, Ana Bratic, Helene Bruhn, Timo E.S. Kauppila, Bertil Macao, Florian A. Schober, Nicole Lesko, Rolf Wibom, Karin Naess, Inger Nennesmo, Anna Wedell, Bradley Peter, Christoph Freyer, Maria Falkenberg, Anna Wredenberg
A multi-systemic mitochondrial disorder due to a dominant p.Y955H disease variant in DNA polymerase gamma
published pages: 2515-2525, ISSN: 0964-6906, DOI: 10.1093/hmg/ddx146
Human Molecular Genetics 26/13 2019-06-18
2018 Ali Al-Behadili, Jay P Uhler, Anna-Karin Berglund, Bradley Peter, Mara Doimo, Aurelio Reyes, Sjoerd Wanrooij, Massimo Zeviani, Maria Falkenberg
A two-nuclease pathway involving RNase H1 is required for primer removal at human mitochondrial OriL
published pages: 9471-9483, ISSN: 0305-1048, DOI: 10.1093/nar/gky708
Nucleic Acids Research 46/18 2019-08-29
2019 Örjan Persson, Yazh Muthukumar, Swaraj Basu, Louise Jenninger, Jay P. Uhler, Anna-Karin Berglund, Robert McFarland, Robert W. Taylor, Claes M. Gustafsson, Erik Larsson, Maria Falkenberg
Copy-choice recombination during mitochondrial L-strand synthesis causes DNA deletions
published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-019-08673-5
Nature Communications 10/1 2019-08-29
2018 Bradley Peter, Geraldine Farge, Carlos Pardo-Hernandez, Stefan TÃ¥ngefjord, Maria Falkenberg
Structural basis for adPEO-causing mutations in the mitochondrial TWINKLE helicase
published pages: 1090-1099, ISSN: 0964-6906, DOI: 10.1093/hmg/ddy415
Human Molecular Genetics 28/7 2019-08-29

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