The MAGE (Melanoma antigen) family consists of 35 proteins in humans that contain a "MAGE homology domain" (MHD) but have widely differing functions. The Smc5-6 complex, which functions in DNA repair, consists of MAGEG1-Nse1 heterodimer. Taking, Nse1 is a putative RING finger E3 ubiquitin ligase, there are two other reports of MAGE proteins interacting with RING-finger proteins. In addition, our structure predictions suggest that part of MHD has similarities to cullin components of E3 ligases. We will test the hypothesis that MAGE proteins are cofactors in E3 ligase complexes. We will carry out structural analyses of the MHD fold using NMR spectroscopy and X-ray crystallography to test our structural predictions. We will mutate critical residues in MAGEG1, that we predict to interact with Nse1, to see if this specifically destroys this interaction and affects DNA repair. We will search for and analyze new RING partners interacting with MAGE proteins to find out MHD common features.

Publications