Fig. 1. The relationship among autophagy, DNA synthesis, and replication stress.

Upon oncogene-induced tumorigenesis, autophagy activation provides the cancer cells with a stable pool of deoxyribonucleotides triphosphate (dNTPs), which sustain a high-rate of DNA synthesis, typical of cancer cells. This intense DNA replication causes Replication Stress (RS), which in turn triggers the DNA Damage Response (DDR). As a result of the DDR activation, autophagy is further enhanced, in order to help the cells to cope with the RS. In addition to oncogene-induced tumorigenesis, HydroxyUrea (HU) treatment can also cause RS, and trigger the above mentioned activation cascades. An intriguing possibility is the hypothetical relevance for autophagy in providing a ribonucleotides triphosphate (NTP) pool, derived by the autophagy-mediated degradation of cellular RNA (RNAphagy).