Fig. 8: Model.

In S-phase HCT-116 and Jurkat cells express increased H2A.X SL mRNA compared to HeLa and RPE-1 cells, so that they synthesise and incorporate more H2A.X protein into the newly made chromatin. Following DNA damage (etoposide treatment or UV irradiation), HeLa cells employ de novo H2A.X synthesis from H2A.X poly(A) mRNA to provide sufficient H2A.X for efficient γH2A.X signalling. In contrast, HCT-116 cells already contain sufficient H2A.X in chromatin to signal DNA damage, so obviating the need for de novo H2A.X synthesis.