Prof. Dr. Dominik Boos

Molecular Genetics II

University of Duisburg-Essen

Phone: +49 201 183 4132
Email

Accurate and complete genome replication is central for genetic homeostasis and requires exact control of replication origin firing, the process of generating replication forks. Higher eukaryotic genomes have thousands of replication origins, whose firing regulation in both unperturbed and DNA damage conditions guarantees genetic stability: A) In unperturbed cell cycles origin firing is tightly coupled to S phase. B) Firing must be efficient to avoid non-replicated gaps. C) Coordination of firing with chromatin processes such as transcription avoids conflict. D) In DNA damage conditions, origin firing becomes globally inhibited to prevent mutation, yet even more, normally dormant, origins fire in actively replicating genome regions to avoid non-replicated gaps due to forks stalling at DNA lesions.

We investigate the regulation step of replication origin firing, pre-initiation complex (pre-IC) formation to understand how vertebrate cells switch between different cell states, S phase vs. G1 phase and unperturbed vs. DNA damage conditions, respectively. Biochemical reconstitution from purified components and replicating Xenopus egg extracts will reveal molecular processes of pre-IC formation and regulation by cell cycle and DNA damage kinases. Human tissue culture will be used for complementary in vivo experiments.