Genetik
Final Report Abstract
Somatic hypermutation is a physiologically very important but mechanistically highly enigmatic process ensuring variability and adaptation of humoral immune responses. The three major areas of research in my lab concern the regulation of the enzyme AID, which damages immunoglobulin genes during hypermutation, the mechanism and regulation of the repair pathways that process the resultant DNA lesions, and the regulation of the balance between DNA damage and repair in germinal centers. Within the report period, we have made considerable progress in all three areas. Concerning AID regulation, we could identify interesting interaction partners and a fascinating new pathway of AID regulation. Concerning DNA repair, we have completed a study on the role of homologous recombination in hypermutating cells, and have sucessfully continued our analyses of the role of factors of the Rad6 pathway in somatic hypermutation. In the area of (de)regulation of hypermutation, we could show that overexpression of the proto-oncogene c-Myc contributes to constitutive somatic hypermutation in lymphomas, and that the tumor suppressor p53 regulates somatic hypermutation and selection in germinal centers. The results from our studies will lead to further investigations of the role and regulation of AID and DNA repair factors in somatic hypermutation, as well as in their role in genetic and epigenetic plasticity of stem cells during aging.
Publications
- Expression of activation-induced cytidine deaminase in malignant lymphomas infiltrating the bone marrow. Appl Immunohistochem Mol Morphol. 2008 Dec;16(6):521-9.
Engels K, Jungnickel B, Tobollik S, Hansmann ML, Kriener S, Willenbrock K
- Non-conservative homologous recombination in human B lymphocytes is promoted by activationinduced cytidine deaminase and transcription. Nucleic Acids Res. 2008 Oct;36(17):5591-601. Epub 2008 Aug 30
Mierau M, Drexler GA, Kutzera A, Braunschmidt K, Ellwart J, Eckardt-Schupp F, Fritz E, Bachl J, Jungnickel B
- The expression of activation induced cytidine deaminase in follicular lymphoma is independent of prognosis and stage. Histopathology. 2009 Mar;54(4):509-12
Willenbrock K, Renné C, Rottenkolber M, Klapper W, Dreyling M, Engelhard M, Küppers R, Hansmann ML, Jungnickel B
- c-Myc overexpression promotes a germinal center-like program in Burkitt's lymphoma. Oncogene. 2010 Feb 11;29(6):888-97. Epub 2009 Nov 2
Scheller H, Tobollik S, Kutzera A, Eder M, Unterlehberg J, Pfeil I, Jungnickel B
- Ubc13 dosage is critical for immunoglobulin gene conversion and gene targeting in vertebrate cells. Nucleic Acids Res. 2010 Aug;38(14):4701-7. Epub 2010 Mar 11
Ertongur I, Tomi NS, Kutzera A, Fischer-Burkart S, Jungnickel B
