MEIG1 is an Important Component of the DNA Damage Response

A hallmark of cancer is genome instability leading to various genetic changes. Each cancer patient has a unique combination of genetic changes, challenging the ability to apply one efficient treatment to different cancers. Meig1 is a highly conserved gene, first identified in mouse spermatocytes undergoing meiotic recombination. Meig1-KO male mice have an aberrant ability to properly repair physiologically induced DNA breaks, that enable recombination, leading to apoptosis and lack of mature sperm. Increased occurrence of tumors has been observed in Meig1-KO mice, hypothesizing that this might be due to delayed or aberrant damage response in Meig1-KO mice, thus increasing genome instability. Indeed, delayed γH2AX recovery was evident in Meig1-KO MEFs, compared to WT-MEFs, after treatment with the DSB-inducing drug Phleomycin. Likewise, 53BP1 foci formation was hampered, and foci disappearance was significantly delayed, after treatment with Phleomycin, in Meig1-KO cells compared to control cells. Using the damage site labeling technique, to follow repair kinetics of oxidative damage in Meig1-KO cells vs. Meig1-KO cells expressing recombinant Meig, it was evident that repair was significantly more efficient in Meig1 expressing cells. In a NHEJ assay, where a break was introduced into a GFP expressing plasmid in a way that GFP could be expressed only upon repair of the break, we found that Meig1-KO cell had a significantly reduced ability to repair the plasmid, compared to control cells. Moreover, expressing recombinant Meig1 in KO cells restored the repair ability to control levels, reinforcing the role of MEIG1 in the NHEJ repair pathway of DSBs.