Structural and functional studies of SUMO ylation and poly-ubiquitination

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Attachment of SUMO (Small ubiquitin-like modifier) family proteins is a post-translational modification that regulates the functions, structures or localizations of modified proteins, and regulates a vast arrays of cellular functions, such as transcription, DNA repair and regulation of chromatin structures. One of the target proteins, Thymine DNA glycosylase (TDG) is an DNA glycosylase that is thought to excise mismatch base from DNA containing G-U or G-T base pairs. SUMO-1 or SUMO-2/3 attachment of TDG has been proposed to promote its dissociation from DNA containing an abasic site.We have determined the crystal structure of the central region of TDG, which involves the catalytic core domain and the SUMOylation site, conjugated to SUMO-1 (SUMO-1-TDG) or SUMO-3 (SUMO-3-TDG). The structure of SUMO-1-TDG shows that the central region of TDG interacts SUMO-1 through both covalent and non-covalent contacts, which seemingly induces a structural rearrangement in a region of TDG. A model building assumes that this possible structural change may create a protrusion on the protein surface, which is positioned so as to make a steric clash with DNA bound to TDG. The structure of SUMO-3-TDG is similar to that of SUMO-1-TDG.