Selenoprotein H protects against oxidative DNA damage in the nucleus

Selenoprotein H (SelH), a newly identified selenoprotein, is a nuclear protein known to protect cancer and neuronal cells from oxidative stress and radiation exposure. These previous results prompt us to propose that SelH acts as a guardian of genome maintenance against oxidative stress. To test this hypothesis, we employed shRNA approaches to create SelH stable knockdown in normal (MRC‐5) and cancer (HeLa, HCT116, and HCT116 with hMLH1 complementation) cell lines. We then assessed the response of the cells to oxidative and other clastogens, including H 2 O 2 , paraquat, neocarzinostatin, hydroxyurea, aphidicolin, and camptothecin, by direct cell counting and colony‐forming assay. We found that SelH shRNA cells showed increased sensitivity to oxidative stress inducing agents paraquat and H 2 O 2 , but to a much less extent to other clastogens. Oxdative stress and DNA breaks activate the ataxia‐telangiectasia mutated (ATM) kinase and transmit signals to downstream repair and checkpoint pathways. Compared to control scrambled shRNA cells, SelH shRNA cells showed increased ATM pathway activation, as evidenced by increased phospho‐ATM Ser‐1981 formation and G2/M blockage 24 h after exposure to H 2 O 2 (20μM). Taken together, SelH may be a critical nuclear selenoprotein that specifically suppresses oxidative stress to maintain genome stability. Grant Funding Source : NA