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Ahmed, E.A.* ; Rosemann, M. ; Scherthan, H.*

NHEJ contributes to the fast repair of radiation-induced DNA double-strand breaks at late Prophase I telomeres.

Health Phys. 115, 102-107 (2018)
DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Dna ; Dna-pk ; Genetic Effects ; Radiation ; Meiosis ; Nhej ; Radiation Damage ; Repair ; Cellular ; Scid ; Telomere
ISSN (print) / ISBN 0017-9078
e-ISSN 1538-5159
Zeitschrift Health Physics
Quellenangaben Band: 115, Heft: 1, Seiten: 102-107 Artikelnummer: , Supplement: ,
Verlag Lippincott Williams & Wilkins
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Radiation Biology (ISB)