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J Pineal Res. 2017 Aug;63(1). doi: 10.1111/jpi.12416. Epub 2017 May 18.

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

Author information

1
Solid Tumor Research Center, Urmia University of Medical Sciences, Urmia, Iran.
2
Department of Orthopedic Surgery, School of Medicine and Shohada Educational Hospital, Tabriz University of Medical Sciences, Tabriz, Iran.
3
Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
4
Health Promotion Research Center, Iran University of Medical Sciences, Tehran, Iran.
5
Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, TX, USA.
6
Institute for Stem Cell and Regenerative Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
7
Students Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.
8
Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
9
Molecular Targeting Therapy Research Group, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
10
Department of Clinical Biochemistry and Laboratory Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.

Abstract

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.

KEYWORDS:

DNA; cancer; chemotherapy; circadian rhythm; genome stability; pineal gland

PMID:
28439991
DOI:
10.1111/jpi.12416
[Indexed for MEDLINE]

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