Melatonin: A pleiotropic molecule that modulates DNA damage response and repair pathways

DNA repair is responsible for maintaining the integrity of the genome. Perturbations
in the DNA repair pathways have been identified in several human cancers. Thus,
compounds targeting DNA damage response (DDR) hold great promise in cancer
therapy. A great deal of effort, in pursuit of new anticancer drugs, has been devoted
to understanding the basic mechanisms and functions of the cellular DNA repair
machinery. Melatonin, a widely produced indoleamine in all organisms, is associated
with a reduced risk of cancer and has multiple regulatory roles on the different aspects
of the DDR and DNA repair. Herein, we have mainly discussed how defective
components in different DNA repair machineries, including homologous recombination
(HR), nonhomologous end-joining
(NHEJ), base excision repair (BER), nucleotide
excision repair (NER), and finally DNA mismatch repair (MMR), can contribute
to the risk of cancer. Melatonin biosynthesis, mode of action, and antioxidant effects
are reviewed along with the means by which the indoleamine regulates DDR at the
transduction, mediation, and functional levels. Finally, we summarize recent studies
that illustrate how melatonin can be combined with DNA-damaging
agents to improve
their efficacy in cancer therapy