Spelbrink

JMtDNA is organized in foci, termed nucleoids, as small assemblies containing 2-10 mtDNA copies and various proteins that are poorly conserved in evolution. Despite a renewed interest in mtDNA due to its involvement in human disease and ageing, there are still many fundamental questions surrounding faithful copying (replication), repair and inheritance of mtDNA in humans. My laboratory aims to address these questions in part via the identification and characterization of those mitochondrial proteins that are part of nucleoids or play a role in their biology, that is to say we concentrate on the machineries in the cell and the mitochondrion that are involved in the maintenance of mtDNA in all its aspects. Ultimately, the aim is to not only understand the very basic molecular biology of for example mtDNA replication and repair and individual nucleoid proteins but to also understand mtDNA maintenance at the cell biological and organismal level. This will not only provide fundamental insight in one of the least understood processes in the cell, it will also provide a framework to understand and possibly treat mtDNA disease.

Hans Spelbrink has recently moved with his research to Nijmegen to join the Institute for Genetic and Metabolic Disease and the NCMLS having been awarded an NWO ALW VICI grant. Prior to his move, he and his research group were at the Institute of Medical Technology in Tampere, Finland where he is still a part-time professor in Molecular Cell Biology and is associated with theFinMIT Academy of Finland Centre of Excellence.

• Spelbrink JN. Functional organization of mammalian mitochondrial DNA in nucleoids: history, recent developments, and future challenges. IUBMB Life. 62:19-32, 2010.

• Duxin JP, Dao B, Martinsson P, Rajala N, Guittat L, Campbell JL, Spelbrink JN, Stewart SA. Human Dna2 is a Nuclear and Mitochondrial DNA Maintenance Protein. Mol Cell Biol. 29:4274-82, 2009.

• Goffart S, Cooper HM, Tyynismaa H, Wanrooij S, Suomalainen A, Spelbrink JN. Twinkle mutations associated with autosomal dominant progressive external ophthalmoplegia lead to impaired helicase function and in vivo mtDNA replication stalling. Hum Mol Genet. 18:328-40, 2009. 

• Cooper HM, Spelbrink JN. The human Sirt3 protein deacetylase is exclusively mitochondrial. Biochem J. 411:279-85, 2008.

• Wanrooij S, Goffart S, Pohjoismäki JL, Yasukawa T, Spelbrink JN. Expression of catalytic mutants of the mtDNA helicase Twinkle and polymerase POLG causes distinct replication stalling phenotypes. Nucleic Acids Res. 35:3238-51, 2007.