As indicated by the MLH1/MSH3 reconstitution and depletion studies, the genetic interaction of WRN and MMR genes cannot readily be recapitulated using isogenic cell models and thus seems to be distinct from acute and hard-wired synthetic lethal interactions, such as described in cancer cells for the alternate BAF complex ATPases SMARCA2/SMARCA4 or the cohesin subunits STAG1/STAG2 (Oike et al., 2013; van der Lelij et al., 2017; Benedetti et al., 2017). This evidence concerns the gene MLH1 and cancer.