5hmC is actively enriched at endogenous DNA damage sites in cancer cell lines
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DNA damage induced by aphidicolin or microirradiation increases 5hmC locally
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TET2 is required to create damage-associated 5hmC foci in HeLa cells
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TET enzymes promote genome integrity under replication stress in mouse ES cells
Summary
5-hydroxymethylcytosine (5hmC) is a DNA base created during active DNA demethylation by the recently discovered TET enzymes. 5hmC has essential roles in gene expression and differentiation. Here, we demonstrate that 5hmC also localizes to sites of DNA damage and repair. 5hmC accumulates at damage foci induced by aphidicolin and microirradiation and colocalizes with major DNA damage response proteins 53BP1 and γH2AX, revealing 5hmC as an epigenetic marker of DNA damage. Deficiency for the TET enzymes eliminates damage-induced 5hmC accumulation and elicits chromosome segregation defects in response to replication stress. Our results indicate that the TET enzymes and 5hmC play essential roles in ensuring genome integrity.