GENOME STABILITY

The eukaryotic genome is transcribed by RNA polymerase 2 (Pol 2). Pol 2 mediated transcription is a tightly controlled process to ensure correct temporal and spatial regulation of gene expression, which is crucial for proper cell function. However, the DNA template that is transcribed by Pol 2 is compromised on a daily basis by numerous types of DNA-damaging factors. DNA damage can block or strongly impede Pol 2 mediated transcription. If these transcription-blocking DNA lesions (TBLs) are not properly resolved, this will severely disrupt cellular homeostasis due to the disturbed synthesis of new RNA molecules. In addition, TBLs may result in genome instability, severe cellular dysfunction or premature cell death, which finally may result in DNA damage-induced accelerated aging. Cells counteract these harmful effects by specifically removing TBLs by transcription-coupled repair (TCR), thereby safeguarding transcription. The severe developmental, neurological and premature aging..

Primary location: Rotterdam Netherlands