Abstract
<jats:p>Genome integrity is fundamental to cellular and organismal health, with the germline genome bearing the most profound impact. During spermatogenesis, post-meiotic germ cells, called spermatids, undergo a series of morphological changes over an extended period (a week in fruit flies, two weeks in humans) to yield mature sperm. Having undergone consecutive meiotic divisions, these spermatids lack homologous chromosomes or sister chromatids, critical templates for accurate DNA repair. How genome integrity of spermatids is ensured during this vulnerable yet prolonged period remains poorly understood. In this study, we show that the process of spermatogenesis is specifically compromised to eliminate damaged nuclei upon γ-irradiation. We further find a non-canonical role of histone variant H2Av in the process of spermatid elimination. Our findings demonstrate the presence of a haploid-specific quality control program that ensures the integrity of the sperm genome transmitted to the next generation.</jats:p>