Arne Klungland's group

Laboratory for Genome repair and regulation

 

Institute of Medical Microbiology, Section for Molecular Biology, is localised at Rikshospitalet, Gaustad, Oslo University Hospital. Four different research groups are colocalised, concentrating on Genome stability and regulation studies, Cancer and Huntingtons Disease, microbiology and biocomputing.

I was fortunate to do my PhD and post doctoral training with Erling Seeberg (Oslo) and Nobel prize laureate 2015 Tomas Lindahl (London), two pioneers in the discovery of fundamental processes for the repair of DNA damage. During these years, we focused on the mechanistic insight in the repair of alkylated, deaminated and oxydized bases in DNA and to develop biological systems to assess their endogenous levels and character (EMBO J 1992, 1996, 1997, Mol Cell 1999, PNAS 1999). Most studies aim to identify genes required for DNA (in)stability and their role in human diseases such as Cancer and Huntington’s disease (Nature 2007, Canc Res 2008, PLoS Genet 2020, Hum Mol Gen 2012, J Clin Invest 2012).

Throughout my independent career we have continued to focus on the role of novel modifications in DNA and RNA and to identify genes required for their dynamic regulation. Yet, our focus has been adapted to regulatory modifications and to unravel the biological function of their readers and erasers (EMBO 2006, 2007, Mol Cell 2013, Nat Comm 2011, 2013, Genes & Dev 2015). 

A broad repertoire of modifications is known to underlie adaptable coding and structural function of proteins, DNA and various RNA species. Methylations of mammalian DNA and histone residues are known to regulate transcription and the discoveries of demethylases that remove methylation in DNA and histones provide a basis for the understanding of dynamic regulation of mammalian gene expression. The reversions of methyl marks on DNA and proteins have been extensively studied the last decade. On the contrary, reversal of N6-methyladenosine (m6A) to adenosine (A) in messenger RNA (mRNA) was only identified recently (for the obesity risk gene, FTO). 6-methyladenine (m6A) is the most abundant internal base modification of messenger RNA (mRNA) in higher eukaryotes. We have identified a second m6A demethylase for mRNA (Zheng et al., Molecular Cell). Internal m6A is the most common modification of mRNA in higher eukaryotes. Male mice lacking Alkbh5 have elevated m6A levels in total mRNA and are characterized by impaired fertility resulting from apoptosis that affects meiotic metaphase-stage spermatocytes. The discovery of this RNA demethylase strongly suggests that the reversible m6A modification has fundamental and broad functions in mammalian cells and in human disease.



Currently we have MSc, PhD students and post docs from more than 10 different countries.

Contact information:
Professor Arne Klungland,Department of Molecular Microbiology A3.3021, Oslo University Hospital, Rikshospitalet, Sognsvannsveien 20, NO-0372 Oslo, Norway,

Tel: +47 23074072, Fax: +47 23074061, E-mail: arne.klungland@medisin.uio.no