The 53BP1-EXPAND1 connection in chromatin structure regulation.

The mammalian interphase chromatin responds to DNA damages by altering the compactness of its architecture, thereby permitting local access of DNA repair machineries. Adding to the cellular strategies of chromatin remodeling following DNA damage, our recent work identified the 53BP1-EXPAND1 module in promoting chromatin dynamics in response to DNA double-strand breaks. Endowed with a nucleosome-binding PWWP domain, EXPAND1 tethers to the chromatin where it is involved in maintaining basal chromatin accessibility in unperturbed cells. Interestingly, through its direct interaction with the DNA damage mediator protein 53BP1, EXPAND1 accumulates at the damage-modified chromatin and triggers its further decondensation. These observations, together with the fact that EXPAND 1 promotes cell survival following DNA damage, suggest that the chromatin-bound factor may facilitate DNA repair by regulating the organization of chromatin structure.