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Post-meiotic DNA double-strand breaks occur in Tetrahymena, and require Topoisomerase II and Spo11.


ABSTRACT: Based on observations of markers for DNA lesions, such as phosphorylated histone H2AX (?H2AX) 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 Tetrahymena thermophila. 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.

SUBMITTER: Akematsu T 

PROVIDER: S-EPMC5482572 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Post-meiotic DNA double-strand breaks occur in <i>Tetrahymena</i>, and require Topoisomerase II and Spo11.

Akematsu Takahiko T   Fukuda Yasuhiro Y   Garg Jyoti J   Fillingham Jeffrey S JS   Pearlman Ronald E RE   Loidl Josef J  

eLife 20170616


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 ci  ...[more]

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