Figure 8

A schematic representation of the main results obtained. (A) SUMO-1 covalent conjugation to K330 leads to a change in the C-terminal conformation of TDG. SUMO-1 thereby also interacts with SBM2. TDG-RD is not displaced from the TDG-CAT domain and hence can rest in its "closed" conformation. Sumoylation thereby influences third party interactions with the RD and therefore "locks" the RD. The presence of free SUMO-1, just as covalent SUMO-1 addition to "open" TDG conformers, increases especially G:U turnover rates ("primed"). Note that also SUMO-modified proteins might be recruited to TDG via SBM2 and have similar effects on TDG's turnover rate. SUMO, when bound via SBM2, sterically competes with TDG-RD for the TDG-CAT surface. The TDG-RD hence adopts a partially "open" conformation which leads to increased G:U repair activity. Also, when SUMO is bound to the SBM2 site, the C-terminus of TDG adopts a conformation similar to the one in the sumoylated protein. The enzymatic turnover especially on G:U mismatches is enhanced through the DNA interaction of either SBM2 recruited or covalently attached SUMO-1. Note that the effect in the case of transient SBM2 interaction is likely due to a local concentration effect as it does not require prolonged SBM2 binding by SUMO. (B) SUMO-1 conjugation or binding to the SBM2 might also occur post-repair once TDG has been trapped on its abasic G:- product to salvage TDG activity by overcoming product inhibition. In the case of non-covalently bound SUMO-1 alternatively a third protein carrying the SUMO-1 group might bring SUMO-1 sufficiently close to TDG for the 'salvage' effect.