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Melatonin: A pleiotropic molecule that modulates DNA damage response and repair pathways
Author(s) -
Majidinia Maryam,
Sadeghpour Alireza,
Mehrzadi Saeed,
Reiter Russel J.,
Khatami Nasrin,
Yousefi Bahman
Publication year - 2017
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/jpi.12416
Subject(s) - dna repair , dna damage , nucleotide excision repair , biology , homologous recombination , melatonin , dna mismatch repair , microbiology and biotechnology , genome instability , non homologous end joining , dna , genetics , cancer research , neuroscience
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.