Highly efficient base excision repair (BER) in human and rat male germ cells

The quality of germ cell DNA is critical for the fate of the offspring, yet there is limited knowledge of the DNA repair capabilities of such cells. O ne of the main DNA repair pathways is base excision repair (BER) which is i nitiated by DNA glycosylases that excise damaged bases, followed by incisio n of the generated abasic (AP) sites. We have studied human and rat methylp urine-DNA glycosytase (MPG), uracil-DNA glycosylase (UNG), and the major AP endonuclease (HAP1/APEX) in male germ cells. Enzymatic activities and west ern analyses indicate that these enzymes are present in human and rat male germ cells in amounts that are at least as high as in somatic cells. Minor differences were observed between different cellular stages of rat spermato genesis and spermiogenesis. Repair of methylated DNA was also studied at th e cellular level using the Comet assay, The repair was highly efficient in both human and rat male germ cells, in primary spermatocytes as well as rou nd spermatids, compared to rat mononuclear blood cells or hepatocytes, This efficient BER removes frequently occurring DNA lesions that arise spontane ously or via environmental agents, thereby minimising the number of potenti al mutations transferred to the next generation.