Bodil Merete Kavli
Background and activities
DNA repair and adaptive immunity
How is DNA lesions generated and repaired in our genome? What is the molecular link between DNA repair and adaptive immunity? What goes wrong when normal cells accumulate mutations and are converted to cancer cells? These are important questions in my research.
I have for many years worked within the field of DNA repair and genome stability with specific focus on repair of genomic uracil (deaminated cytosine). The work includes structural and functional characterization of the uracil-DNA glycosylases UNG and SMUG1 (Biochemistry 1995; Cell 1995; Nature 1996; Embo J 1996, 2000, 2008; JBC 2002; NAR 2007, 2011; JBC 2011: DNA repair 2012).
Studies of immune-deficient patients with mutations in the UNG gene revealed an essential role of this enzyme also in adaptive immunity (Nature Immunology 2003; JEM 2005). Here, the UNG glycosylase plays a central role in processing of enzymatically introduced uracil at the Ig loci to achieve affinity maturation of antibodies.
The primary and physiologically role of activation-induced cytidine deaminase (AID), the master enzyme in adaptive immunity, is to introduce uracil lesions at the Ig loci to initiate antibody diversification.
However, AID and other members of this mutator-protein family (APOBECs) pose a great threat to genomic integrity and mistargeted AID activity is likely a major cause behind oncogenic mutations and translocations in B-cell lymphomas as well as other cancers. Understanding regulation of these dynamic genome processes has during the last years become my major research interest (Nat Struct Mol Biol 2009; JMB 2013; Exp Cell Research 2014; DNA repair 2015).