Project 4 Functions and regulations of the replication initiation regulator TopBP1 upon exposure to IR

Principal Investigator

Prof. Dr. rer. nat. Dominik Boos

Molekulare Genetik II
Universität Duisburg-Essen

Dominik.Boos@uni-due.de

 

 

Summary

DNA replication is both a target of the DNA damage checkpoint and a checkpoint activator: failure of the checkpoint to inhibit the initiation of DNA replication upon IR exposure is known as radio-resistant DNA synthesis, and many other replication processes need regulation to ensure sufficiently accurate genome duplication despite DNA damage. Moreover, replication forks stall at DNA lesions, which activates the S phase DNA damage checkpoint. The Boos lab investigates how the initiation of DNA replication, a major step of replication control, occurs and is regulated, and how it contributes to cancer formation. In the next years research will focus on a main regulation hub of initiation, the TopBP1-Treslin-MTBP protein complex that: 1. is essential for initiation, 2. makes initiation specific to S phase, 3. consists of components that are targets and mediators of the DNA damage response. As part of this RTG Prof. Boos will investigate how replication initiation and DNA damage processes are coordinated via the TopBP1-Treslin-MTBP regulation platform in human cells exposed to IR. Specifically, he will address how TopBP1, which is at the crossroads of DSB repair, DNA damage signaling and replication initiation, cooperates with its novel interactor SMARCAD1, a chromatin remodeler required for IR-induced DSB repair

 

Selected Publications

Koehler K, Ferreira P, Pfander B, Boos D* Regulation of initiation of DNA replication upon DNA damage in eukaryotes.; Chapter in the textbook The Initiation of DNA Replication in Eukaryotes, 2016* corresponding author

Boos D, Yekezare M and Diffley JFX. Identification of a heteromeric complex that promotes DNA replication origin firing in human cells. Science 2013 May 24; 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 Jul 12; 21(13):1152-7

Boos D*, Frigola J* and Diffley JFX.  Activation of the replicative DNA helicase: breaking up is hard to do. Curr Op Cell Biol 2012, 24:1–8  * equal contribution