ad-51, rad-54, mus-101, atl-1, but not rad-50), and also the npp-15 ortholog of human NUP133, a mammalian nuclear pore component [44], conferred radiosensitivity. In contrast to other HDR genes, rad-50 knockdown in mutant glp-1(ar202) doesn’t boost radiosensitivity in mitotic germline tumors, even though rad-50 gene expression was reduced right after RNAi by 81% in ar202 (S3 Fig), indicating that C. elegans RAD-50 might not play a function in radiation-induced DSB repair in mitotic germ cells. This result is consistent with findings from Villeneuve and co-workers that showed RAD-50 is expected for loading RAD-51 onto radiation-induced DSBs in meiotic but not mitotic germ cells [45]. Detailed analysis of influence of inactivating rad-51 and mre-11 revealed significantlyincreased sensitivity of glp-1(ar202) germ cells among 60-300Gy, decreasing 50% tumor Acetylene-linker-Val-Cit-PABC-MMAE biological activity handle dose from 266 to 168Gy with rad-51 RNAi (Fig 3B, left; p0.01) and to 105Gy for mre-11 RNAi (Fig 3B, right; p0.01). Differences in tumor response were detectable at 24h after 210Gy (Fig 3C; p0.01), and at 120h rad-51-inactivated worms displayed 74% lowered germ cell quantity (two,973 vs. 782 GSCs/gonad), although mre-11 inactivation almost eradicated tumor. In addition, mre-11 RNAi remedy was associated with extension of ar202 lifespan postirradiation, comparable to that of wild-type unirradiated worms (Fig 3D). In contrast to HDR genes, silencing genes of canonical NHEJ (cku-80 and lig-4), cell cycle, DNA damage checkpoint, DNA replication and chromatin remodeling had no effect on ar202 germline tumor radiosensitivity (Fig 3A and Table 1). RNAi conferred comparable radiation responses in germ cells inside the distal area of wild-type worms, enhancing radiosensitivity at 60Gy, an ineffective dose in N2 worms (not shown), upon knockdown of HDR (mre-11, rad-51, rad-54, mus-101 and atl-1; Fig 3E), but not NHEJ (lig-4 and cku-80) genes. To address whether or not ar202 germline tumors express NHEJ genes, we employed the temperature-sensitive germ cell-deficient mutant glp-4(bn2)[46]. S1 Table shows that when glp-4(bn2) animals are grown in the permissive temperature, and hence contain a germ line, they express essential NHEJ genes lig-4 and cku-80, at the same time as HDR genes mus-101, rad-51 and atl-1, at a lot greater levels than animals grown in the restrictive temperature, which lack a germ line. Gene expression levels in somatic tissue and germ line could also be affected by culturing animals in the diverse temperatures, although this can be unlikely in our study. We conclude, for that reason that NHEJ genes are, in fact, enriched inside the germ line, while post-mitotic somatic cells in adult worms express minimal amounts. Constant with these information, we lately reported mitotically-active cells of murine compact intestinal crypts aggressively repair radiation DNA damage, though post-mitotic villus cells do not [23]. To obtain functional proof 
that RNAi feeding adequately inactivated respective NHEJ DSB repair genes, we examined consequence of inactivating NHEJ genes on somatic development in irradiated wild-type worms. For these research, N2 embryos grown in lig-4 RNAi plates had been collected at 4h post egg laying, a time preceding vulval development, and irradiated with 120Gy. At 96h soon after 120Gy, minimal all round damage was detected in N2 worms even with rad51 silencing, even though lig-4 or cku-80 knockdown-worms displayed abnormal vulval development (Fig 3F, upper panel, p0.01 for lig-4; p0.05 for cku-80), with improved penetrance of somatic defects (l