16 April 2019

Publication in Nature Communications

Structural basis of specific H2A K13/K15 ubiquitination by RNF168

Genetics does not tell the whole story. Epigenetics play crucial roles in the regulation of gene expression and DNA repair by installing specific chemical marks on the chromatin fibre that contains our genome. For example, proper DNA repair relies on the attachment of a small ubiquitin protein to a selective site on histone H2A in chromatin. Reseachers from the groups of Hugo van Ingen (NMR Group, Bijvoet Center) and Titia Sixma (Netherlands Cancer Institute) show in a publication in Nature Communications how this site is selected.

Using advanced NMR methods and validated by a combination of techniques they could show exactly how the choice is made and how a point  mutation can selectively prevent this ubiquitin attachment. As this mutation was recently shown to frequently occur in cancer, suggest that its role in DNA repair is important for tumorigenesis. The fact that tumours use genetic mutations to beat epigenetic regulation is nice illustratrion of the intricate interplay between genetics and epigenetics in health and disease.