Sumoylation: A new wrestler in the DNA repair ring

Abstract

E ukaryotic cells contain three essential complexes with heterodimers of Smc (structural maintenance of chromosomes) proteins at their core, namely cohesin, condensin, and the Smc5-6 complex. These complexes perform structural roles on chromosomes related to different DNA metabolic processes, in the case of Smc5-6 damage repair. However, two groups working independently, Zhao and Blobel (1) as described in this issue of PNAS, and Watts and colleagues (2), have demonstrated that, unlike in cohesin and condensin complexes, one of the non-Smc subunits of the Smc5-6 complex also possesses an enzymatic activity. Mms21/Nse2 is the third SUMO E3 ligase in the yeast genome besides the known ligases Siz1 and Siz2. SUMO conjugate targets for Mms21/Nse2 include other subunits of the Smc5-6 complex as well as repair proteins like Ku70. The implication of these findings is that the Smc5-6 complex not only has a structural function, but is also capable of handling biochemical activities, perhaps reflecting an overall function in recognition of DNA structures and activation of repair pathways. Eukaryotic proteins are subjected to a wide range of posttranslational modifications including the covalent attachment of proteins. Ubiquitin is the most familiar of the proteinaceus modifiers, and the enzymology of its activation and transfer has been extensively studied. Recently, several ubiquitin-related proteins have been identified and shown to form covalent attachments to proteins. One of the most intriguing of these is SUMO (small ubiquitin-related modifier). In vertebrates, there are several variants of SUMO (SUMO-1, -2, and -3), whereas only one (Smt3p) has been found in the budding yeast Saccharomyces cerevisiae . Smt3p becomes attached to targets through a multistep process that requires an activating (E1-activating enzyme), a conjugating (E2-conjugating enzyme), and a ligating (E3-ligase) enzyme (3). So far, two E3 SUMO ligases have been described in S. cerevisiae , …