Figure 6: Model of palindrome-mediated translocation in humans.

Cruciform extrusion leads to the sequential cleavage by GEN1 and Artemis. The diagonal cleavage produces a nick at the base of the cruciform, which is sealed by intrinsic ligase activity in the model system. The resulting closed hairpin leads to random selection of the template strand for MMR, manifesting frequent proximal–distal exchanges at the junction of the rearranged molecules. In contrast, a hairpin with a residual nick at the base of the cruciform could produce a bias in template-strand selection for the MMR reaction, resulting in a lower incidence of proximal–distal exchanges at the junction of de novo translocations in sperm.