5-Hydroxymethylcytosine Marks Sites of DNA Damage and Promotes Genome Stability

Publication date: Available online 4 February 2016
Source:Cell Reports
Author(s): Georgia Rose Kafer, Xuan Li, Takuro Horii, Isao Suetake, Shoji Tajima, Izuho Hatada, Peter Mark Carlton
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.

Graphical abstract

Teaser

Kafer et al. demonstrate that DNA damage causes the modified DNA base 5-hydroxymethylcytosine (5hmC) to become locally enriched over broad chromosomal domains and that the TET enzymes promote correct chromosome segregation during replication stress.


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