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Through its functions in chromosome replication, segregation, and repair, the Smc5/6 complex has a central role in the maintenance of genome stability. The complex is part of the family of structural maintenance of chromosome protein complexes that also includes cohesin and condensin. Mutations in any of these complexes disrupt chromosome segregation and render cells hypersensitive to different types of DNA damage. The chromosome mis-segregation phenotypes in cohesin and condensin mutants can be attributed to their functions in sister chromatid cohesion and chromosome condensation, respectively. Cohesin-dependent chromatid cohesion is also needed for DNA double-strand break repair, whereas condensin is required for repair of single-strand breaks. How Smc5/6 promotes chromosome stability is largely unknown. Accumulating data suggest that it prevents accumulation of aberrant DNA links between sister chromatids created during repair by homologous recombination. A long-standing idea is that it also has a role in the maintenance of nondamaged chromosomes. Here, we present an overview of the current knowledge of Smc5/6 and discuss a possible nonrepair role of the complex.

The Smc5/6 Complex: More Than Repair?