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Claudia Lukas

Claudia Lukas

Programleder

Claudia Lukas's research at the Novo Nordisk Center for Protein Research aims at understanding fundamental mechanisms of genome integrity in mammalian cells and how these mechanisms are subverted in cancer. Specifically, she is interested in identification and functional characterization of protein pathways and their regulators that guard the human genome against DNA damage as cells transcribe, replicate and segregate their chromosomes during the cell cycle.

Aktuel forskning

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

• 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)





 



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