Rad50 mediates DNA demethylation to establish pluripotent reprogramming
Hanseul Park, Byounggook Cho, Jongpil Kim
Abstract
DNA demethylation is characterized by the loss of methyl groups from 5-methylcytosine, and this activity is involved in various biological processes in mammalian cell development and differentiation. In particular, dynamic DNA demethylation in the process of somatic cell reprogramming is required for successful iPSC generation. In the present study, we reported the role of Rad50 in the DNA demethylation process during somatic cell reprogramming. We found that Rad50 was highly expressed in pluripotent stem cells and that Rad50 regulated global DNA demethylation levels. Importantly, the overexpression of Rad50 resulted in the enhanced efficiency of iPSC generation via increased DNA demethylation, whereas Rad50 knockdown led to DNA hypermethylation, which suppressed somatic cell reprogramming into iPSCs. Moreover, we found that Rad50 associated with Tet1 to facilitate the DNA demethylation process in pluripotent reprogramming. Therefore, our findings highlight the novel role of Rad50 in the DNA demethylation process during somatic cell reprogramming.