A chemical on/off switch for DNA damage repair

A chemical on/off switch for DNA damage repair

Cells have a complex protein machinery that activates a repair response after detecting damaged DNA. One of the mechanisms used to regulate the function and localisation of these proteins is the addition of molecules onto their building blocks (amino acids) that modify their behaviour.

Work from Ivan Ahel’s lab, together with collaborators at the Max Planck Institute in Cologne (Germany), has revealed that serine is the preferred amino acid of a family of modifying enzymes responsible for ADP-ribosylation (ADPr) – a protein modification regulating cellular processes, including the vital activation of DNA repair responses at DNA breaks. Palazzo et al. used cell biology and biochemical approaches to show that serine residues of histones (proteins that package DNA) become the main ADPr sites after DNA damage. Together with their previous work identifying the ‘eraser’ of serine ADPr, which enables the process to be reversed, this shows how proteins involved in DNA damage repair can be switched on/off in different physiological and pathological conditions. This knowledge could be used to develop new cancer drugs regulating ADPr signals and, therefore, controlling DNA repair. 

Anna Caballe

Palazzo L, Leidecker O, Prokhorova E, Dauben H, Matic I, Ahel I. (2018).

Elife 7. pii: e34334. doi: 10.7554/eLife.34334.