We have shown that, rather than boosting levels of RAD51 on treatment with cisplatin, in a possibly unsuccessful attempt to repair high levels of ICLs encountered at stalled replication forks by the protracted HRR process, melanoma cells instead shut down HRR and boost levels of endonucleases, such as ERCC1-XPF, that can rapidly unhook crosslinks encountered prior to, and possibly also during replication but before replication fork arrest, and then use translesion synthesis DNA polymerases to allow replication to proceed. Here, RAD51 is linked to melanoma.