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The Role of SIRT1 on DNA Damage Response and Epigenetic Alterations in Cancer

Department of Pharmacology, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo 04039-032, Brazil
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Int. J. Mol. Sci. 2019, 20(13), 3153; https://doi.org/10.3390/ijms20133153
Received: 30 April 2019 / Revised: 3 June 2019 / Accepted: 6 June 2019 / Published: 28 June 2019
(This article belongs to the Special Issue Sirtuins and Epigenetics in Aging and Diseases)
Sirtuin-1 (SIRT1) is a class-III histone deacetylase (HDAC), an NAD+-dependent enzyme deeply involved in gene regulation, genome stability maintenance, apoptosis, autophagy, senescence, proliferation, aging, and tumorigenesis. It also has a key role in the epigenetic regulation of tissue homeostasis and many diseases by deacetylating both histone and non-histone targets. Different studies have shown ambiguous implications of SIRT1 as both a tumor suppressor and tumor promoter. However, this contradictory role seems to be determined by the cell type and SIRT1 localization. SIRT1 upregulation has already been demonstrated in some cancer cells, such as acute myeloid leukemia (AML) and primary colon, prostate, melanoma, and non-melanoma skin cancers, while SIRT1 downregulation was described in breast cancer and hepatic cell carcinomas. Even though new functions of SIRT1 have been characterized, the underlying mechanisms that define its precise role on DNA damage and repair and their contribution to cancer development remains underexplored. Here, we discuss the recent findings on the interplay among SIRT1, oxidative stress, and DNA repair machinery and its impact on normal and cancer cells. View Full-Text
Keywords: SIRT1; DNA damage/repair; epigenetics; cancer development SIRT1; DNA damage/repair; epigenetics; cancer development
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Alves-Fernandes, D.K.; Jasiulionis, M.G. The Role of SIRT1 on DNA Damage Response and Epigenetic Alterations in Cancer. Int. J. Mol. Sci. 2019, 20, 3153.

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