The 53BP1-EXPAND1 connection in chromatin structure regulation

Abstract

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 EXPAND1 promotes cell survival following DNA damage, suggest that the chromatin-bound factor may facilitate DNA repair by regulating the organization of chromatin structure.

Acknowledgements

This work was supported in part by grants from the National Institutes of Health (CA089239, CA092312 and CA100109 to J.C.) and from Seed Funding for Basic Research (Project Code: 200908159008; HKU to M.S.Y.H.). M.S.Y.H. would like to thank J.C. for his continuous support. J.C. is a recipient of an Era of Hope Scholar award from the Department of Defence and a member of the Mayo Clinic Breast SPORE program (P50 CA116201).

Figures and Tables

Figure 1 Proposed model of EXPAND1 in chromatin structure regulation. (A) EXPAND1 associates with chromatin through its ability to interact with nucleosomes. (B) DNA damage triggers the accumulation of EXPAND1 to sites of DNA breaks. (C) Binding of EXPAND1 to chromatin domains surrounding DNA break site opens up its structure. (D) Efficient loading of DNA repair proteins to the damage-modified chromatin. For simplicity, 53BP1 is omitted from illustration (see text).