Protein Signaling Program
Blegdamsvej 3, 2200 København N, Bygning 6, Bygning: 06-1-40
Research Interests: Quantitative cellular imaging of DNA repair and mechanisms of genome integrity maintenance
Claudia Lukas´s longstanding research interest is to study mechanisms and pathways of human genome integrity maintenance, which are crucial for the prevention of human pathologies such as cancer and premature ageing. Her key experimental approach to study these pathways is cellular imaging. Here, cellular responses to exogenous genotoxic challenges or endogenous errors in DNA replication, mitosis and DNA repair can be profiled in a high-content, quantitative fashion on a single cell basis. In addition, spatial-temporal dynamics of DNA repair pathways can be directly visualized and quantified using fluorescent protein mobility and localisation data from living cells.
Claudia Lukas is also the Head of the Protein Imaging Platform at the Novo Nordisk Foundation for Protein Research, where she coordinates a team of microscopy and image analysis experts.
Claudia Lukas's approach to discover novel genome caretakers is to functionally ablate every single human gene using RNA interference combined with automated high-content microscopy and quantitative image analysis. This technology was key to discover a novel, major regulator of DNA double strand break repair, the RNF168 ubiquitin ligase, as well as two of its regulators (TRIP12 and UBR5), that through proteolytic degradation balance the levels of this rate-limiting enzyme.
Other approaches she has been using to unravel mechanisms of genome stability include real-time imaging of spatio-temporal behavior of DNA repair proteins directly in living cells. Using high-resolution fluorescence time-lapse microscopy, the fate of a single DNA lesion can be tracked from its origin all the way to its repair and restoration of the neighboring chromatin. The key achievement obtained by this approach was a visual evidence that a fraction DNA lesions caused by replicative stress can only be resolved after mitotic passage into the next cell cycle.
Finally, she is very interested to develop novel assays for high-content imaging approaches in order to move closer towards unbiased, quantitative cell biology.
Most significant publications
Primary research publications
R, S. Pedersen., Karemore, G., Gudjonsson, T., Rask, M. B., Neumann, B., Heriche, J. K., Pepperkok, R., Ellenberg, J., Gerlich, D. W., Lukas, J., and Lukas, C. (2016) Profiling DNA damage response following mitotic perturbations, Nat Commun7, 13887.
Ochs, F., Somyajit, K., Altmeyer, M., Rask, M. B., Lukas, J., and Lukas, C. (2016) 53BP1 fosters fidelity of homology-directed DNA repair, Nat Struct Mol Biol23, 714-721.
• Gudjonsson, T., Altmeyer, M., Savic, V., Toledo, L., Dinant, C., Grøfte, M., Bartkova, J., Poulsen, M., Oka, Y., Bekker-Jensen, S., Mailand, N., Neumann, B., Heriche, J.-K., Shearer, R., Saunders, D., Bartek, J, Lukas, J., Lukas, C. TRIP12 and UBR5 suppress spreading of chromatin ubiquitylation at damaged chromosomes. Cell 150, 607-709 (2012)
• Lukas, C., Savic, V., Beker-Jensen, S., Doil, C., Neumann, B., Pedersen, R. S., Grofte, M., Chan, K. L., Hickson, I. D., Bartek, J., and Lukas, J. 53BP1 nuclear bodies shield DNA lesions generated by mitotic transmission of underreplicated chromosomes. Nat. Cell Biol. 13, 243-253 (2011)
• Doil, C., Mailand, N., Bekker-Jensen, S., Menard, P., Larsen, D. H., Pepperkok, R., Ellenberg, J., Panier, S., Durocher, D., Bartek, J., Lukas, J., and Lukas, C. RNF168 binds and amplifies ubiquitin conjugates on damaged chromosomes to promote accumulation of repair proteins. Cell 136, 435-446 (2009)
• Mailand, N., Bekker-Jensen, S., Faustrup, H., Melander, F., Bartek, J., Lukas, C., and Lukas, J. The RNF8 ubiquitin ligase promotes assembly of repair proteins at the DNA damage-modified chromatin. Cell 131, 887-900 (2007)
• Bartkova, J., Horejsi, Z., Koed, K., Guldberg, P., Krämer, A., Sehested, M., Nesland, J., Lukas, C., Ørntoft, T., Lukas, J., and Bartek. J. DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis. Nature 434, 864-870 (2005)
• Sartori, A. A., Lukas, C., Coates, J., Fu, S., Bartek, J., Baer, R., Lukas, J., and Jackson, S. P. CtIP cooperates with the MRE11 complex to promote DNA resection. Nature 450, 509-514 (2007)
• Lukas, C., Falck, J., Bartkova, J., Bartek, J., and Lukas, J. Distinct spatio-temporal dynamics of mammalian checkpoint regulators induced by DNA damage. Nat. Cell Biol. 5, 255-260 (2003)
Reviews and opinion articles
• Lukas, J., Lukas, C., and Bartek, J. More than just a focus: Chromatin response to DNA damage and its role in genome integrity maintenance. Nat. Cell Biol. 13, 1161-1169 (2011)
• Bartek, J., Lukas, C., and Lukas, J. Checking on DNA damage in S phase. Nat. Rev. Mol. Cell Biol. 5, 792-805 (2004)