Protein Signaling Program
Blegdamsvej 3, 2200 København N, Bygning 6, Building: 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 current research interest is to understand the sources of spontaneous, endogenously generated DNA damage, which is autonomously occurring in cells and is considered the major cause of genomic instability and cancer. Her previous work and the work from other labs has pointed the finger strongly to DNA replication as a key source of endogenous DNA damage (Lukas et al, Nat Cell Biol, 2011). In a follow-up study of this, she and her colleagues in the lab of Jiri Lukas then identified the process of cellular division, or mitosis, as another key source of genomic instability (Pedersen et al, Nat Comm 2016). Here, she discovered a novel type of replication stress that occurs with a temporal delay after cell division failure associated with whole-genome doubling or tetraploidy. Her current activities are focusing mostly on the underlying molecular mechanisms of such tetraploidy-induced DNA damage and the potential implications for cell fate decisions, such as differentiation and quiescence. In addition, Claudia and her colleagues in Jiri Lukas lab are working intensively on understanding the role of chromatin architecture in DNA repair (with Postdoc Fena Ochs; Ochs et al, NSMB 2016) and how the repair of some DNA lesions can stretch over several cell cycles and cell generations (with Postdoc Julian Spies and Associate Professor Kai Neelsen).
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)