The ubiquitous MRG/MORF family of proteins is involved in cell senescence, or the terminal loss of proliferative potential, a model for aging and tumor suppression at the cellular level. These proteins are defined by the ∼20 kDa MRG domain that binds a plethora of transcriptional regulators and chromatin-remodeling factors, including the histone deacetylase transcriptional corepressor mSin3A and the novel nuclear protein PAM14, and they are also known components of the Tip60/NuA4 complex via interactions with the MRG binding protein (MRGBP). We present here the crystal structure of a prototypic MRG domain from human MRG15 whose core consists of two orthogonal helix hairpins. Despite the lack of sequence similarity, the core structure has surprisingly striking homology to a DNA-interacting domain of the tyrosine site-specific recombinases XerD, λ integrase, and Cre. Site-directed mutagenesis studies based on the X-ray structure and bioinformatics identified key residues involved in the binding of PAM14 and MRGBP. ©2006 Elsevier Ltd All rights reserved.
Bowman, B. R., Moure, C. M., Kirtane, B. M., Welschhans, R. L., Tominaga, K., Pereira-Smith, O. M., & Quiocho, F. A. (2006). Multipurpose MRG domain involved in cell senescence and proliferation exhibits structural homology to a DNA-interacting domain. Structure, 14(1), 151–158. https://doi.org/10.1016/j.str.2005.08.019