Project 2 Mechanisms of the p97- and ubiquitin-governed radiation response
Prof. Dr. Hemmo Meyer
Dept. of Molecular Biology
University of Duisburg-Essen
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 analyze how Cdc48/p97 may link radiation-induced DNA damage to cell cycle progression and ask if it protects from cell death.
van den Boom J, Wolf M, Weimann L, Schulze N, Li F, Kaschani F, Riemer A, Zierhut C, Kaiser M, Iliakis G, Funabiki H, Meyer H. VCP/p97 extracts sterically trapped Ku70/80 rings from DNA in double strand break repair. Mol. Cell, 64, 1-10, October 6, 2016.
Eiteneuer A., Seiler J., Weith M., Beullens M., Lesage B., Krenn V., Musacchio A., Bollen M., Meyer H. Inhibitor-3 ensures bipolar mitotic spindle attachment by limiting association of SDS22 to kinetochore-bound protein phosphatase-1. EMBO J., 2014, 33:2704-20
Riemer A, Dobrynin G, Dressler A, Bremer S, Soni A, Iliakis G, Meyer H. The p97-Ufd1-Npl4 ATPase complex ensures robustness of the G2/M checkpoint by facilitating CDC25A degradation. Cell Cycle, 2014, 13:919-27
Meyer H, Bug M, Bremer S. Emerging functions of the VCP/p97 AAA-ATPase in the ubiquitin system. Nat. Cell Biol. 2012, 14:117-23.
Meerang M, Ritz D, Paliwal S, Garajova Z, Bosshard M, Mailand N, Janscak P, Hüscher U, Meyer H, Ramadan K. The ubiquitin-selective segregase VCP/p97 orchestrates the response to DNA double strand breaks. Nat. Cell Biol., 2011, 13:1376-82
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.