Gene Modification Linked To DNA Repair

The 5hmC epigenetic modification could be used as a marker of DNA damage in detecting cancers, researchers say.

AsianScientist (Feb. 22, 2016) – A team of scientists in Japan has found that a DNA modification called 5-hydroxymethylcytosine (5hmC) localizes at sites of DNA damage and repair. This gene switch is thus closely linked to DNA repair and may play a role in preventing cancer. Their work is published in Cell Reports.

To turn genes on or off, a methyl group can be added to or removed from DNA. During the removal of this chemical tag, called demethylation, the methyl group is converted to 5hmC as an intermediate step. Ten-eleven translocation enzymes, or TETs for short, are thought to be critical to the demethylation process.

The researchers from Kyoto University found that 5hmC localizes near breaks in DNA, both those that may develop naturally or are caused by DNA-damaging drugs or irradiation. The team further found that inhibiting TET enzymes in cells resulted in a lack of 5hmC, followed by errors in chromosome separation. This suggests that TET enzymes are important for the production of 5hmC at DNA damage sites and that both play critical roles in responding to DNA damage.

Recent research has shown that 5hmC is also associated with an ‘opening up’ of nearby chromatin, the tightly packaged assembly of proteins and DNA in the cell nucleus. The present study raises the possibility that 5hmC helps to keep chromatin ‘open’ so it can be more accessible to other DNA damage response proteins. 5hmC could be used as a marker for DNA damage, according to the researchers.

“Our results imply that loss of TET enzymes and 5hmC depletion could contribute significantly to genome instability and inaccurate chromosome segregation, perhaps explaining the correlation of low 5hmC levels with cancer,” said the researchers.

The article can be found at: Kafer et al. (2016) 5-Hydroxymethylcytosine Marks Sites of DNA Damage and Promotes Genome Stability.

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Source: Kyoto University; Photo: Bruce Rolff/123RF.
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