2010/06/01

The structure of the cellular stress sensor Gadd45α has been determined by NMR

The Gadd45 nuclear proteins modulate the response of mammalian cells to genetoxic and physiological stress. Gadd45 regulate DNA repair, cell cycle, apoptosis, and modulate tumor formation by interacting with other proteins. Human Gadd45α is predominantly monomeric and folds into an α/β structure with two long flexible regions. The mitotic kinase Aurora-A interacts through its non-kinase N-terminal domain with a region of Gadd45α encompassing the site of dimerization. This result suggest that the oligomerization of Gadd45α could be a regulatory mechanism to modulate its interactions with Aurora-A, and possibly with other proteins too. However Gadd45α appears to interact only weakly with the protein DNA sliding clamp Proliferating Cell Nuclear Antigen, in contrast with previous reports.