Function of DNA-protein kinase catalytic subunit during the early meiotic prophase without Ku70 and Ku86.
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.
Hamer
Geert
G
Department of Endocrinology, Faculty of Biology, Utrecht University, 3584 CH Utrecht, The Netherlands. g.hamer@bio.uu.nl
Roepers-Gajadien
Hermien L
HL
van Duyn-Goedhart
Annemarie
A
Gademan
Iris S
IS
Kal
Henk B
HB
van Buul
Paul P W
PP
Ashley
Terry
T
de Rooij
Dirk G
DG
D000818:Animals; D034961:Antigens, Nuclear / Q000096:biosynthesis / Q000378:metabolism*; D017209:Apoptosis / Q000528:radiation effects; D004249:DNA Damage; D004265:DNA Helicases; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000378:metabolism*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D000072200:Ku Autoantigen; D008297:Male; D008540:Meiosis / Q000502:physiology* / Q000528:radiation effects; D051379:Mice; D016513:Mice, SCID; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D012670:Seminiferous Epithelium / Q000201:enzymology / Q000378:metabolism* / Q000528:radiation effects*; D013090:Spermatocytes / Q000473:pathology; D013093:Spermatogonia / Q000166:cytology / Q000528:radiation effects; D014965:X-Rays
D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D051747:DNA-Activated Protein Kinase; C497264:Prkdc protein, mouse; D017346:Protein Serine-Threonine Kinases; D004265:DNA Helicases; C106893:XRCC5 protein, human; C000606512:Xrcc5 protein, mouse; C000606509:Xrcc6 protein, human; C000606510:Xrcc6 protein, mouse; D000072200:Ku Autoantigen