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. 2022 Mar 8;12(3):417. doi: 10.3390/biom12030417

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© 2022 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

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TET1 stimulates the activity of PARP1 independently of DNA damage. Poly(ADP-ribosyl)ation of TET1 by PARP1 increases TET1 enzymatic activity and regulates the hydroxylase activity of the DNA demethylation processes. Poly(ADP-ribosyl)ation of TET1 preserves the unmethylated state and activates the transcription of oncogenes. The PARP1 inhibitor inhibits the enzymatic activity of TET1, as a result, the expression of oncogenes is downregulated due to hypermethylation. Availability of NAD⁺ makes SIRT6 enzymatically active to remove the acetyl group from histone proteins, further downregulating the transcription of oncogenes.