Exposure of cells to ionizing radiation induces DNA double-strand breaks. To 
repair double-strand breaks correctly, cells must distinguish between the ends 
of chromosomes (telomeres) and DNA double-strand breaks within chromosomes. 
Double-strand breaks in telomeric DNA may lead to telomere shortening and 
mutagenesis. Eukaryotic cells repair double-strand breaks primarily by two 
mechanisms: error-free homologous recombination and error-prone nonhomologous 
end joining, of which homologous recombination is used in early meiotic prophase 
I to create recombined haploid gametes by two meiotic cell divisions lacking an 
intervening S-phase. Genotoxic exposures put meiosis at risk to transmit 
mutations, and ionizing radiation is known to induce large double-strand 
break-marking phospho (gamma)-H2AX foci along the cores and ends of mouse 
meiotic chromosomes. However, it remained unclear through which repair pathway 
the ionizing radiation-induced telomeric double-strand breaks are repaired in 
late prophase I spermatocytes. Using male wild-type and nonhomologous end 
joining-deficient (severe combined immunodeficient) mice, this study 
investigated the kinetics of in vivo double-strand break formation and repair at 
telomeres of late prophase I chromosomes up to 12 h after 0.5 Gy of whole-body 
gamma irradiation. Late pachytene and diplotene spermatocytes revealed 
overlapping gamma-H2AX and telomere repeat signal foci, indicating telomeric DNA 
damage. The comparison of double-strand break repair rates at telomeres and 
internal prophase chromosome sites revealed a more rapid double-strand break 
repair at wild-type telomeres during the first hour after irradiation. Increased 
double-strand break foci numbers at nonhomologous end joining-deficient 
telomeres and chromosomes and a slowed repair rate in this DNA-dependent protein 
kinase catalytic subunit mutant suggest that the fast repair of double-strand 
breaks in telomeric DNA repeats during late prophase I is largely mediated by 
canonical nonhomologous end joining.