Physiological Chemistry

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Gyula Timinszky

Chromatin dynamics during the DNA damage response

The integrity of the genetic information is constantly under threat by environmental factors. Cells rapidly respond to DNA damage by activating vital DNA damage signaling and repair mechanisms. Mutations in genes encoding proteins with functions in the cellular response to DNA damage from recognition to repair predispose to cancer development.

Chromatin poses a formidable challenge to the DNA repair machinery in eukaryotes. Since DNA is packaged into nucleosomes and nucleosomes carry epigenetic information, which ideally needs to be faithfully inherited following DNA repair in order to maintain cell fate, the DNA repair machinery uses chromatin remodeling factors to promote accurate repair. PARylation is central for the regulation of a number of chromatin modifying proteins – the histone chaperone FACT, the chromatin remodelers CHD4 and Alc1, as well as Polycomb group proteins – that switch function upon DNA damage and recruit to or leave loci of damaged DNA.