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

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Akematsu, Takahiko, Fukuda, Yasuhiro, Garg, Jyoti, Fillingham, Jeffrey S, Pearlman, Ronald E, Loidl, Josef
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2017
Materias:
Cell Biology
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5482572/
https://www.ncbi.nlm.nih.gov/pubmed/28621664
http://dx.doi.org/10.7554/eLife.26176
_version_ 1783245588552220672
author Akematsu, Takahiko
Fukuda, Yasuhiro
Garg, Jyoti
Fillingham, Jeffrey S
Pearlman, Ronald E
Loidl, Josef
author_facet Akematsu, Takahiko
Fukuda, Yasuhiro
Garg, Jyoti
Fillingham, Jeffrey S
Pearlman, Ronald E
Loidl, Josef
author_sort Akematsu, Takahiko
collection PubMed
description 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 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. DOI: http://dx.doi.org/10.7554/eLife.26176.001
format Online
Article
Text
id pubmed-5482572
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher eLife Sciences Publications, Ltd
record_format MEDLINE/PubMed
spelling pubmed-54825722017-06-26 Post-meiotic DNA double-strand breaks occur in Tetrahymena, and require Topoisomerase II and Spo11 Akematsu, Takahiko Fukuda, Yasuhiro Garg, Jyoti Fillingham, Jeffrey S Pearlman, Ronald E Loidl, Josef eLife Cell Biology 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 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. DOI: http://dx.doi.org/10.7554/eLife.26176.001 eLife Sciences Publications, Ltd 2017-06-16 /pmc/articles/PMC5482572/ /pubmed/28621664 http://dx.doi.org/10.7554/eLife.26176 Text en © 2017, Akematsu et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Cell Biology
Akematsu, Takahiko
Fukuda, Yasuhiro
Garg, Jyoti
Fillingham, Jeffrey S
Pearlman, Ronald E
Loidl, Josef
Post-meiotic DNA double-strand breaks occur in Tetrahymena, and require Topoisomerase II and Spo11
title Post-meiotic DNA double-strand breaks occur in Tetrahymena, and require Topoisomerase II and Spo11
title_full Post-meiotic DNA double-strand breaks occur in Tetrahymena, and require Topoisomerase II and Spo11
title_fullStr Post-meiotic DNA double-strand breaks occur in Tetrahymena, and require Topoisomerase II and Spo11
title_full_unstemmed Post-meiotic DNA double-strand breaks occur in Tetrahymena, and require Topoisomerase II and Spo11
title_short Post-meiotic DNA double-strand breaks occur in Tetrahymena, and require Topoisomerase II and Spo11
title_sort post-meiotic dna double-strand breaks occur in tetrahymena, and require topoisomerase ii and spo11
topic Cell Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5482572/
https://www.ncbi.nlm.nih.gov/pubmed/28621664
http://dx.doi.org/10.7554/eLife.26176
work_keys_str_mv AT akematsutakahiko postmeioticdnadoublestrandbreaksoccurintetrahymenaandrequiretopoisomeraseiiandspo11
AT fukudayasuhiro postmeioticdnadoublestrandbreaksoccurintetrahymenaandrequiretopoisomeraseiiandspo11
AT gargjyoti postmeioticdnadoublestrandbreaksoccurintetrahymenaandrequiretopoisomeraseiiandspo11
AT fillinghamjeffreys postmeioticdnadoublestrandbreaksoccurintetrahymenaandrequiretopoisomeraseiiandspo11
AT pearlmanronalde postmeioticdnadoublestrandbreaksoccurintetrahymenaandrequiretopoisomeraseiiandspo11
AT loidljosef postmeioticdnadoublestrandbreaksoccurintetrahymenaandrequiretopoisomeraseiiandspo11

Ejemplares similares