Meig1 is a highly conserved gene first identified in mouse pachytene spermatocytes undergoing meiotic recombination. In these cells the MEIG1 protein enters the nucleus and forms foci along the meiotic chromosomes, reminiscent of foci obtain by proteins known to be involved in the DNA damage response. Meig1 knockout (KO) male mice are infertile. These mice exhibit significantly fragmented DNA in late pachytene spermatocytes, as well as in the few epididymal sperm cells that could be obtained, and increased apoptosis of post recombination spermatogenic cells, probably due to improperly repaired meiotic double strand breaks (DSB). Interestingly, most Meig1 KO mice (more than 30 mice to date), and about one third of the Meig1 +/- heterozygotes developed huge and aggressive tumors between 6-14 months of age, whereas none of the age-matched wild-type (WT) mice developed tumors. Given these findings we hypothesize that MEIG1 plays a role in maintaining genome integrity. To further investigate the potential role of MEIG1 in the DNA damage response we exposed WT and KO MEFs to genotoxic treatments such as UV radiation (254 nm, 50mJ/cm2) and etoposide treatment (50µM), and examined the kinetics of γH2AX signaling in these cells. KO MEFs exhibited significantly slower disappearance of the γH2AX foci compare to WT MEFs, following both treatments, suggesting delayed or aberrant repair. Moreover, in U2OS cell (human osteosarcoma cells) Meig1 expression was significantly up-regulated soon after exposure to etoposide, whereas following UV radiation Meig1 up-regulation was delayed concomitant to the appearance of DSB. Altogether, these results suggest that MEIG1 is indeed a new player involved in the DNA damage response, especially in the response to DSB.
