VERTEBRATE DNA REPLICATION
Dr. Dominik Boos
Since 2014: Independent group leader ZMB, Essen
2007-2014: Postdoc in the lab of John Diffley, LRI Clare Hall Laboratories, UK
2002-2007: PhD thesis in the lab of Olaf Stemmann, MPI for Biochemistry, Martinsried, Germany
We investigate fundamental molecular mechanisms and regulations of DNA replication. The focus is on vertebrate tissue culture cells because little is known in higher eukaryotes about this. The lab is particularly interested in the initiation step of replication, as this is a pivotal step of regulation of replication in a variety of cellular contexts. Appropriately controlled initiation: 1) couples replication to the S phase of the cell cycle, 2) regulates replication upon DNA damage, and 3) mediates the right temporal control of cellular replication. Thus, the proper regulation of initiation critically determines efficiency and accuracy of genome duplication.
In the next years the lab will concentrate on a major regulation hub of replication initiation, the Treslin-MTBP-TopBP1 protein complex. We investigate aspects of its molecular and cellular functions, regulations in unperturbed cell cycles and upon DNA damage, as well as its impact on cancer formation.
We mainly use human tissue culture, RNAi and various cell biological and biochemical techniques to analyse protein functions. We complement this by in vitro biochemistry for insight into molecular details. In the future we may also use Xenopus egg extracts as a biochemically tractable model system.
Boos D, Yekezare M and Diffley JFX. Identification of a heteromeric complex that promotes DNA replication origin firing in human cells. Science 2013, 340, 981-983.
Boos D, Sanchez-Pulido L, Rappas M, Pearl LH, Oliver AW, Ponting CP and Diffley JFX. Regulation of DNA Replication through Sld3-Dpb11 Interaction Is Conserved from Yeast to Humans. Curr Biol 2011, 21, 1152-1157.
Boos D*, Frigola J* and Diffley JFX. Activation of the replicative DNA helicase:breaking up is hard to do. Review; Curr Op Cell Biol 2012, 24, 1–8. (*equal contribution)