DNA is the prime target of anticancer treatments. DNA damage triggers a series of signaling cascades promoting cellular survival, including DNA repair, cell cycle arrest, and autophagy. The elevated basal and/or stressful levels of both DNA repair and autophagy observed in tumor cells, in contrast to normal cells, have been identified as the most important drug-responsive programs that impact the outcome of anticancer therapy. The exact relationship between DNA repair and autophagy in cancer cells remains unclear. On one hand, autophagy has been shown to regulate some of the DNA repair proteins after DNA damage by maintaining the balance between their synthesis, stabilization, and degradation. One the other hand, some evidence has demonstrated that some DNA repair molecular have a crucial role in the initiation of autophagy. In this review, we mainly discuss the interplay between DNA repair and autophagy in anticancer therapy and expect to enlighten some effective strategies for cancer treatment.
Keywords: AMPK, adenosine monophosphate-activated protein kinase; ATG5, autophagy-related gene 5; ATM, ataxia-telangiectasia mutated; ATR, ATM and Rad3-related; BER, base excision repair; Chk1, check-point kinase 1; Chk2, check-point kinase 2; DDR, DNA damage response; DNA damage; DNA damage response; DNA repair; DNA-PKcs, DNA-dependent protein kinase catalytic subunit; DSBs, double-strand breaks; HDAC, histone deacetylases; HR, homologous recombination; IR, ionizing radiation; MGMT, O6 methylguanine –DNA methyltransferase; MMR, mismatch repair; MRN, Mre11-Rad50-Nbs1; NER, nucleotide excision recombination; NHEJ, non-homologous end joining; OGG1, 8-oxoguannine DNA glycosidase; PARP-1, poly (ADP-ribose) polymerase 1; PI3K, phosphoinositide 3-kinase; PML, promyelocytic leukemia; SSBs, single-strand break; TMZ, temozolomide; TSC2, tuberous sclerosis complex 2; anticancer therapy; apoptosis; autophagy; cell cycle arrest; mTOR, mammalian target of rapamycin; γ-H2AX, phosphorylated histone.