Project 3
Cell cycle regulation by the ubiquitin-dependent Cdc48/p97 chaperone system after radiation
Principal Investigator
Prof. Dr. rer. nat. Hemmo Meyer
Dept. of Molecular Biology,
University of Duisburg-Essen
Summary
Proliferating cells respond to radiation-induced DNA damage either by cell cycle arrest or by induction of cell death. The ubiquitin-dependent AAA+-type ATPase Cdc48/p97 has been linked to cell cycle regulation, DNA repair and apoptosis. We will explore the role of Cdc48/p97 and its cofactors in mediating the crosstalk between these processes upon exposure to different doses of ionizing radiation in tumour cells. We will apply live-cell imaging and biochemical approaches to analyse how Cdc48/p97 may link radiation-induced DNA damage to cell cycle progression and ask if it protects from cell death.
Selected Publications
Dobrynin G, Popp O, Romer T, Bremer S, Schmitz MHA, Gerlich DW and Meyer HH. Cdc48/p97(Ufd1-Npl4) antagonizes Aurora B during chromosome segregation in HeLa cells. J Cell Sci 124:1571-80.
Ramadan K, Bruderer R, Spiga F, Popp O, Baur T, Gotta M, and Meyer HH. Cdc48/p97 promotes reformation of the nucleus by extracting Aurora B kinase from chromatin. Nature 2007;450:1258-1262.
Baur R, Ramadan K, Schlundt A, Kartenbeck J, and Meyer HH. NSF- and SNARE-mediated membrane fusion is required for nuclear envelope formation and completion of nuclear pore complex assembly in Xenopus laevis egg extracts. J Cell Sci 2007;120:2895-903.
Isaacson RL, Pye VE, Simpson P, Meyer HH, Zhang X, Freemont PS, Matthews S. Detailed structural Insight into the p97-Npl4-Ufd1 interface. J Biol Chem 2007; 282:21361-2169.
Pye VE, Beuron F, Keetch C, McKeown C, Robinson CV, Meyer HH, Zhang X, and PS Freemont The p97-Ufd1-Npl4 Complex: First Structural Insights. PNAS 2007;104:467-472.