Fig. 7: Model.

Mild replicative stress (i.e., 0.4 µM aphidicolin) and the suppression of late origin firing (i.e., RO3306) may result in substantial under-replication, which is undetected by the G2/M checkpoint. As cells move into mitosis, RAD51 is recruited to ssDNA at replication forks in a manner dependent on PLK1, and protects them from the attack of mitotic nucleases, such as MUS81, hence allowing the completion of DNA replication. This is distinctive from the RAD52-mediated MiDAS, which occurs downstream of mitotic DNA breaks. Centromeric under-replication prevents SAC inactivation until resolved by MiDAS. RAD51-mediated protection of centromeric DNA, which is enriched with PLK1, hence ensures appropriate chromosome segregation.