Fission yeast condensin contributes to interphase chromatin organization and prevents transcription-coupled DNA damage

Genome Biology

David J. Barry¹  Christopher Barrington²  Tereza Gerguri³  Paul A. Bates³  Xiao Fu³  Frank Uhlmann⁴  Bhavin S. Khatri⁵  Yasutaka Kakui⁶ 

[1] Advanced Light Microscopy Science Technology Platform, The Francis Crick Institute, 1 Midland Road, NW1 1AT, London, UK;Bioinformatics & Biostatistics Science Technology Platform, The Francis Crick Institute, 1 Midland Road, NW1 1AT, London, UK;Biomolecular Modelling Laboratory, The Francis Crick Institute, 1 Midland Road, NW1 1AT, London, UK;Chromosome Segregation Laboratory, The Francis Crick Institute, 1 Midland Road, NW1 1AT, London, UK;Chromosome Segregation Laboratory, The Francis Crick Institute, 1 Midland Road, NW1 1AT, London, UK;Department of Life Sciences, Imperial College London, Silwood Park Campus, SL5 7PY, Ascot, UK;Chromosome Segregation Laboratory, The Francis Crick Institute, 1 Midland Road, NW1 1AT, London, UK;Waseda Institute for Advanced Study, Waseda University, 1-21-1, Nishiwaseda, Shinjuku-ku, 169-0051, Tokyo, Japan;

关键词: Condensin;    Chromosome architecture;    Interphase chromatin;    Transcription;    DNA damage;    Polymer physics;    S. pombe;   

DOI  :  10.1186/s13059-020-02183-0

来源: Springer

【 摘 要 】

BackgroundStructural maintenance of chromosomes (SMC) complexes are central organizers of chromatin architecture throughout the cell cycle. The SMC family member condensin is best known for establishing long-range chromatin interactions in mitosis. These compact chromatin and create mechanically stable chromosomes. How condensin contributes to chromatin organization in interphase is less well understood.ResultsHere, we use efficient conditional depletion of fission yeast condensin to determine its contribution to interphase chromatin organization. We deplete condensin in G2-arrested cells to preempt confounding effects from cell cycle progression without condensin. Genome-wide chromatin interaction mapping, using Hi-C, reveals condensin-mediated chromatin interactions in interphase that are qualitatively similar to those observed in mitosis, but quantitatively far less prevalent. Despite their low abundance, chromatin mobility tracking shows that condensin markedly confines interphase chromatin movements. Without condensin, chromatin behaves as an unconstrained Rouse polymer with excluded volume, while condensin constrains its mobility. Unexpectedly, we find that condensin is required during interphase to prevent ongoing transcription from eliciting a DNA damage response.ConclusionsIn addition to establishing mitotic chromosome architecture, condensin-mediated long-range chromatin interactions contribute to shaping chromatin organization in interphase. The resulting structure confines chromatin mobility and protects the genome from transcription-induced DNA damage. This adds to the important roles of condensin in maintaining chromosome stability.

【 授权许可】

CC BY