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Florian Brückner
Membrane Protein Laboratory, Diamond Light Source
Harwell Science and Innovation Campus, Didcot, OX11 0DE
+44-1235-77-8465
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  • Structural and functional studies of the RNA polymerase II elongation complex

RNA polymerase II (Pol II) is the molecular machine at the heart of transcription, the first step in gene expression. Pol II synthesizes all the mRNA in the nucleus of a eukaryotic cell. The transcription cycle consists of initiation, elongation and termination. During the elongation phase Pol II forms a stable complex with template DNA, nontemplate DNA and product RNA, the so-called elongation complex, which allows for processive synthesis of the mRNA.
To obtain insight into various mechanistic aspects of Pol II elongation, we study functional elongation complexes with a combination of x-ray crystallography and in-vitro transcription experiments. My main PhD projects concern the mechanism of DNA lesion recognition and the mechanism of translocation along DNA.
We elucidated the molecular mechanism of the recognition of the thymine dimer DNA photolesion by transcribing Pol II. This type of lesion is a major cause of skin cancer and recognition by Pol II allows the cell efficient repair.
Pol II translocates along the DNA after each nucleotide incorporation into the growing RNA chain in order to transcribe the complete gene in a processive manner. The molecular mechanism of translocation was poorly understood and a subject of debate. During my PhD we succeeded in trapping a possible translocation intermediate in a crystal. Structural analysis of this intermediate suggests the existence of a two-step translocation mechanism.


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  • Kettenberger, H., Eisenfuhr, A., Brueckner, F., Theis, M., Famulok, M., and Cramer, P. (2006). Structure of an RNA polymerase II-RNA inhibitor complex elucidates transcription regulation by noncoding RNAs. Nat Struct Mol Biol 13, 44-48.

    Kashkina, E., Anikin, M., Brueckner, F., Pomerantz, R.T., McAllister, W.T., Cramer, P., Temiakov, D. (2006). Template misalignment in multisubunit RNA polymerases and transcription fidelity. Mol Cell 24, 257-266.

    Brueckner, F., Hennecke, U., Carell, T., Cramer, P. (2007). CPD damage recognition by transcribing RNA polymerase II. Science 315, 859-862.

    Brueckner, F., Cramer, P. (2007). DNA photodamage recognition by RNA polymerase II. FEBS Lett 581, 2757-2760.

    Kashkina, E., Anikin, M., Brueckner, F., Lehmann, E., Kochetkov, S.N., McAllister, W.T., Cramer, P., Temiakov, D. (2007). Multisubunit RNA polymerases melt only a single DNA base pair downstream of the active site. J Biol Chem 282, 21578-21582.

    Korndörfer, I.P., Brueckner, F., Skerra, A. (2007). The crystal structure of the human (S100A8/S100A9)2 heterotetramer, calprotectin, illustrates how conformational changes of interacting alpha-helices can determine specific association of two EF-hand proteins. J Mol Biol 370, 887-898.

    Lehmann, E., Brueckner, F., Cramer, P. (2007). Molecular basis of RNA-dependent RNA polymerase II activity. Nature, 450, 445-449.

    Damsma, G., Alt, A., Brueckner, F., Carell, T., Cramer, P. (2007). Mechanism of transcriptional stalling at cisplatin-damaged DNA. Nat Struct Mol Biol 14, 1127-33.

    Andrecka, J., Lewis, R., Brueckner, F., Lehmann, E., Cramer, P., Michaelis, J. (2008). Single-molecule tracking of mRNA exiting from RNA polymerase II. Proc Natl Acad Sci U S A. 105, 135-140.

    Cramer, P., Armache, K.-J., Baumli, S., Benkert, S., Brueckner, F., Buchen, C., Damsma, G.E., Dengl, S., Geiger, S.R., Jasiak, A.J., Jawhari, A., Jennebach, S., Kamenski, T., Kettenberger, H., Kuhn, C.-D., Lehmann, E., Leike, K., Sydow, J. and Vannini, A. (2008). Structure of Eukaryotic RNA Polymerases. Annu. Rev. Biophys. 37, 337-352.

    Brueckner, F., Cramer, P. Molecular basis of RNA polymerase II translocation. In preparation.


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  • Organization of the "Protein dynamics in health and disease" summer retreat 2006 in Grainau


  • Scientific presentation at the ENB members day in Garching in Oktober 2006 (poster and talk)


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Contact Info

Florian Brückner
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Alumni
Structural Biology
Cramer Lab