Recently discovered targeted therapies for melanoma have shown excellent responses in specific subgroups of patients. However such treatments are beneficial to only a part of melanoma patients and are limited by rapid development of drug resistance, which highlights the need to identify novel therapeutic targets. Cell cycle checkpoints are mechanisms that preserve genomic integrity during cell proliferation by halting the cell cycle, promoting DNA repair and suppressing apoptosis in the presence of DNA abnormalities, such as DNA damage. We have previously reported that almost 70% of melanoma cell lines have a G2 phase checkpoint defect. This defect impairs cell cycle arrest but it’s surprisingly associated with decreased cellular sensitivity to DNA double strand breaks, a type of DNA damage commonly used by chemotherapy to kill cancerous cells. In this work we show that despite the lack of cell cycle arrest, the activity of the main checkpoint response initiators, the ATM and CHK2 kinases, is intact. This is a novelty in the field of cell cycle checkpoint defects, where faulty ATM signalling is often the culprit of impaired arrest. We also show that the defective cells have elevated PLK1 activity and that the checkpoint arrest in these cells can be restored through PLK1 inhibition. This supports dysregulated PLK1 activity to be the cause of the lack of checkpoint arrest. Moreover, we have found that the defective cells have elevated PI3K activity on which they rely for survival and which may contribute to reduce cellular sensitivity to genotoxic stress. We propose that the peculiar mechanism underlying this novel cell cycle checkpoint defect may explain the atypical response to DNA double strand breaks. Elucidation of the molecular mechanisms of this checkpoint defect could contribute to convert chemotherapy, a currently inefficient treatment in melanoma, into a targeted and efficient melanoma therapy.