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The caveat with the study of multi- and poly-SUMOylated proteins or group SUMOylated complexes lies in the difficulty of obtaining loss of function mutants because a) several dozens of lysines can be modified and/or SUMOylation can pass on to another lysine residue upon mutation of the acceptor lysine, b) the SUMO-associated function can arise not from direct SUMOylation, but from non-covalent interaction with SUMO via a SIM domain, and c) within group SUMOylated complexes, simultaneous abrogation of a critical number of SUMO-SIM interactions may be required in order to obtain an effect on the complex [91], and this is more so for assemblies that phase-separate.
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