Abstract:
DNA damage response (DDR) is one of the main mechanisms, by which life counters against exogenous and endogenous oxidative stress induced DNA damage. In an organism, the DDR in different cells and tissues has various levels of activation. . Using the model organism
Caenorhabditis elegans as experimental objects, we constructed a transgenic line for the pharynx-specific expression of
hus-1 gene, upstream of the DDR pathway, and then introduced into
hus-1 mutation background, generating DDR pharynx-specific rescue lines BPL1121, BPL1122 and BPL1123 . The experimental system was used to detect the effect of DDR pharynx rescue on the embryos lethality of γ radiation induced and investigate the effects of heterogeneous activation of DDR on radiation biological effects and its underlying mechanisms. Results showed that the embryonic lethality of irradiated BPL1121 worms increased from 24.72 ± 1.77 to 42.66 ± 1.18 (
P < 0.01) compared with
hus-1 mutant worms, this enhancement continued up to the intact F1 progeny of non-irradiated worms (
P < 0.01), although F2 progeny return to background levels (
P > 0.05). The insulin-like pathway in nematodes is closely related to the growth, development and reproduction behaviors of nematodes, and
daf-2 is a key gene in this signaling pathway. Introducing BPL1121 into the background of
daf-2 mutation, it was found that DAF-2 functional loss significantly inhibited the embryonic radiation lethality of BPL1121 worms. The heterogeneous activation of DDR in pharynx increases the radiation sensitivity of germ cells, and the insulin-like pathway participates in the remote regulation of pharyngeal DDR to radio-sensitivity of germ cells.