The study investigates the role of histone H2AX in genomic stability and DNA repair in mice. H2AX−/− mice exhibit growth retardation, immune deficiency, and infertility, along with chromosomal instability and impaired DNA repair. These phenotypes are associated with defects in the recruitment of specific DNA-repair proteins to irradiation-induced foci, particularly Nbs1, 53bp1, and Brca1, but not Rad51. H2AX is crucial for facilitating the assembly of these repair complexes on damaged DNA. The absence of H2AX does not impair irradiation-induced cell-cycle checkpoints, suggesting that H2AX is essential for recruiting repair proteins to sites of DNA damage rather than for the initial detection of damage. The findings highlight the importance of H2AX in maintaining genomic integrity and the efficiency of DNA repair processes.The study investigates the role of histone H2AX in genomic stability and DNA repair in mice. H2AX−/− mice exhibit growth retardation, immune deficiency, and infertility, along with chromosomal instability and impaired DNA repair. These phenotypes are associated with defects in the recruitment of specific DNA-repair proteins to irradiation-induced foci, particularly Nbs1, 53bp1, and Brca1, but not Rad51. H2AX is crucial for facilitating the assembly of these repair complexes on damaged DNA. The absence of H2AX does not impair irradiation-induced cell-cycle checkpoints, suggesting that H2AX is essential for recruiting repair proteins to sites of DNA damage rather than for the initial detection of damage. The findings highlight the importance of H2AX in maintaining genomic integrity and the efficiency of DNA repair processes.