DNA damage and JIL-1 kinase signaling at active chromatin

• Applicant: Dr. Catherine Regnard, Ph.D.
• Subject Area: General Genetics and Functional Genome Biology ; Biochemistry ; Cell Biology
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 456587778

The part of the genome coding for the actual information of all cellular proteins, representing only a small fraction of the whole genome, probably has dedicated mechanisms ensuring that mutations are repaired most efficiently and error-free. In the projects of this grant proposal, we would like to address how the stability of the coding genome is maintained in response to exogenous and endogenous DNA damage which is constantly challenging the genome. We will study the endogenous DNA damage that is directly introduced by transcription (R-loops) in the active genome as well as the active genome compartment per se when DNA-damage is induced. Indeed, the epigenetic histone modification H3K36me3 specifically marks the coding part (exons) of active genes from humans to flies. Fruit flies have much fewer paralogs than humans for candidate chromatin components, and thus are an ideal model organism for this approach. In addition, we recently showed that an essential kinase complex is specifically targeted to the coding genome by H3K36me3, and we will study the activity of the kinase as well as its interaction network upon DNA-damage. We believe that by combining in vitro reconstitution approaches and analysis of phosphorylated substrates, we will be able to open a new field of research to address the mechanisms maintaining stability of the coding genome.

• DFG Programme: Research Grants