Function of DNA-Protein Kinase Catalytic Subunit During the Early Meiotic Prophase Without Ku70 and Ku86

• Published in: Biology of reproduction Vol. 68; no. 3; pp. 717 - 721
• Main Authors: HAMER, Geert, ROEPERS-GAJADIEN, Hermien L, VAN DUYN-GOEDHART, Annemarie, GADEMAN, Iris S, KAL, Henk B, VAN BUUL, Paul P. W, ASHLEY, Terry, DE ROOIJ, Dirk G
• Format: Journal Article
• Language: English
• Published: Madison, WI Society for the Study of Reproduction 01.03.2003
• Subjects: Animals; Antigens, Nuclear - biosynthesis; Antigens, Nuclear - metabolism; Apoptosis - radiation effects; Biological and medical sciences; Biological effects of radiation; DNA Damage; DNA Helicases; DNA-Activated Protein Kinase; DNA-Binding Proteins - biosynthesis; DNA-Binding Proteins - metabolism; Fundamental and applied biological sciences. Psychology; Immunohistochemistry; In Situ Nick-End Labeling; Ionizing radiations; Ku Autoantigen; Male; Meiosis - physiology; Meiosis - radiation effects; Mice; Mice, SCID; Nuclear Proteins; Protein-Serine-Threonine Kinases - biosynthesis; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - metabolism; Seminiferous Epithelium - enzymology; Seminiferous Epithelium - metabolism; Seminiferous Epithelium - radiation effects; Spermatocytes - pathology; Spermatogonia - cytology; Spermatogonia - radiation effects; Tissues, organs and organisms biophysics; X-Rays; Catalytic subunit; Radiosensitivity; Enzyme; Spermatogenesis; Transferases; Rodentia; Meiosis; Germinal cell; Testicle; Male genital system; X ray irradiation; Signal transduction; Vertebrata; Ionizing irradiation; Mammalia; Spermatocyte; Mouse; Cell death; Protein kinase; Animal; DNA; Spermatogonia; Apoptosis
• ISSN: 0006-3363; 1529-7268
• DOI: 10.1095/biolreprod.102.008920

All components of the double-stranded DNA break (DSB) repair complex DNA-dependent protein kinase (DNA-PK), including Ku70, Ku86, and DNA-PK catalytic subunit (DNA-PKcs), were found in the radiosensitive spermatogonia. Although p53 induction was unaffected, spermatogonial apoptosis occurred faster in the irradiated DNA-PKcs-deficient scid testis. This finding suggests that spermatogonial DNA-PK functions in DNA damage repair rather than p53 induction. Despite the fact that early spermatocytes lack the Ku proteins, spontaneous apoptosis of these cells occurred in the scid testis. The majority of these apoptotic spermatocytes were found at stage IV of the cycle of the seminiferous epithelium where a meiotic checkpoint has been suggested to exist. Meiotic synapsis and recombination during the early meiotic prophase induce DSBs, which are apparently less accurately repaired in scid spermatocytes that then fail to pass the meiotic checkpoint. The role for DNA-PKcs during the meiotic prophase differs from that in mitotic cells; it is not influenced by ionizing radiation and is independent of the Ku heterodimer.