SMC5 and cancer: When the postreplicative Smc5/6 levels are low, cells rely more on structure-specific endonucleases (Figure 4H) that can introduce crossovers and cause genome rearrangements (Gritenaite et al., 2014, Szakal and Branzei, 2013), indicating that low levels of Smc5/6 can predispose in the long run to genomic alterations characteristic of cancers.