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PMID:28621664
Citation |
Akematsu, T, Fukuda, Y, Garg, J, Fillingham, JS, Pearlman, RE and Loidl, J (2017) Post-meiotic DNA double-strand breaks occur in, and require Topoisomerase II and Spo11. Elife 6 |
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Abstract |
Based on observations of markers for DNA lesions, such as phosphorylated histone H2AX (γH2AX) and open DNA ends, it has been suggested that post-meiotic DNA double-strand breaks (PM-DSBs) enable chromatin remodeling during animal spermiogenesis. However, the existence of PM-DSBs is unconfirmed, and the mechanism responsible for their formation is unclear. Here, we report the first direct observation of programmed PM-DSBs via the electrophoretic separation of DSB-generated DNA fragments in the ciliate. These PM-DSBs are accompanied by switching from a heterochromatic to euchromatic chromatin structure in the haploid pronucleus. Both a topoisomerase II paralog with exclusive pronuclear expression and Spo11 are prerequisites for PM-DSB induction. Reduced PM-DSB induction blocks euchromatin formation, characterized by histone H3K56 acetylation, leading to a failure in gametic nuclei production. We propose that PM-DSBs are responsible for histone replacement during the reprogramming of generative to undifferentiated progeny nuclei. |
Links |
PubMed PMC5482572 Online version:10.7554/eLife.26176 |
Keywords |
Chromatin/metabolism; DNA Breaks, Double-Stranded; DNA Topoisomerases, Type II/metabolism; DNA, Protozoan/metabolism; Endodeoxyribonucleases/metabolism; Meiosis; Tetrahymena thermophila/enzymology; Tetrahymena thermophila/physiology |
Significance
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