DMCA
Pathways of DNA double-strand break repair during the mammalian cell cycle (2003)
| Venue: | Mol. Cell. Biol |
| Citations: | 129 - 10 self |
BibTeX
@ARTICLE{Rothkamm03pathwaysof,
author = {Kai Rothkamm and Ines Krüger and Larry H. Thompson and Markus Löbrich},
title = {Pathways of DNA double-strand break repair during the mammalian cell cycle},
journal = {Mol. Cell. Biol},
year = {2003},
pages = {5706--5715}
}
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Abstract
Little is known about the quantitative contributions of nonhomologous end joining (NHEJ) and homologous recombination (HR) to DNA double-strand break (DSB) repair in different cell cycle phases after physiologically relevant doses of ionizing radiation. Using immunofluorescence detection of �-H2AX nuclear foci as a novel approach for monitoring the repair of DSBs, we show here that NHEJ-defective hamster cells (CHO mutant V3 cells) have strongly reduced repair in all cell cycle phases after 1 Gy of irradiation. In contrast, HR-defective CHO irs1SF cells have a minor repair defect in G 1, greater impairment in S, and a substantial defect in late S/G 2. Furthermore, the radiosensitivity of irs1SF cells is slight in G 1 but dramatically higher in late S/G 2, while V3 cells show high sensitivity throughout the cell cycle. These findings show that NHEJ is important in all cell cycle phases, while HR is particularly important in late S/G 2, where both pathways contribute to repair and radioresistance. In contrast to DSBs produced by ionizing radiation, DSBs produced by the replication inhibitor aphidicolin are repaired entirely by HR. irs1SF, but not V3, cells show hypersensitivity to aphidicolin treatment. These data provide the first evaluation of the cell cycle-specific contributions of NHEJ and HR to the repair of radiation-induced versus replication-associated DSBs. DNA double-strand breaks (DSBs) are considered the most biologically damaging lesions produced by ionizing radiation
Keyphrases
dna double-strand break repair mammalian cell cycle v3 cell cell cycle substantial defect minor repair defect immunofluorescence detection novel approach irs1sf cell high sensitivity first evaluation nonhomologous end joining double-strand break relevant dos cell cycle-specific contribution dna double-strand break cell cycle phase h2ax nuclear focus homologous recombination quantitative contribution replication inhibitor aphidicolin damaging lesion different cell cycle phase radiation-induced versus replication-associated dsbs hr-defective cho irs1sf cell nhej-defective hamster cell
