The effect of nobiletin on UV-induced DNA damage responses in yeast

Nobiletin is a dietary phytochemical belonging to polymethoxy flavonoids from the peels of citrus fruits. It has a distinct metabolic feature compared to polyhydroxyflavonoids due to its high bioavailability. Nobiletin is shown to have health beneficial properties, including anti-inflammatory and anti-carcinogenic activities. We investigate how nobiletin affects DNA damage response after UVB treatment in unicellular model organism, baker’s yeast. The results show that nobiletin increases cell survival after UVB damage. UVB treatment induces histone H2A phosphorylation, a marker for DNA damage. The addition of nobiletin can increase both the phosphorylation levels of H2A and phosphotylation levels of Rad53, which is a DNA damage checkpoint protein, after UVB treatment. In the aspects of histone modification, nobiletin has no significant effect on H3K4 trimethylation and it reduces H3K79 trimethylation. Besides, nobiletin increases H3K9 acetylation, which represented that nobiletin promote cell arrest in cell cycle S phase. Furthermore, the addition of nobiletin also has no significant effect on reactive oxygen species (ROS) production after UVB treatment. Our results suggest nobiletin treatment increases the sensitivity of yeast cell to UV damage, promote cell cycle arrest and may facilitate cells to recruit repair proteins to DNA damage sites, thus, influence cell survival.