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Cell biology

TET enzymes (TET1/2/3)

DETET-Enzyme (TET1/2/3)

TET1, TET2, and TET3 are enzymes that erase DNA methylation marks, step by step. (They are iron- and alpha-ketoglutarate-dependent dioxygenases.) They oxidize a methylated DNA base (5-methylcytosine) in stages. First to 5hmC, then 5fC, then 5caC. Those oxidized bases can be cut out (by thymine DNA glycosylase) and replaced via base-excision repair. That gives one route to active DNA demethylation. TET activity depends on oxygen, vitamin C, and TCA-cycle molecules. So it ties these enzymes to your cell's metabolism. One big aging link involves TET2. Loss-of-function mutations in TET2 are among the most common drivers of clonal hematopoiesis (CHIP). CHIP is the age-related expansion of mutant blood-cell clones. And it raises the risk of blood cancers, heart disease, and death.

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