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SAF-A Regulates Interphase Chromosome Structure through Oligomerization with Chromatin-Associated RNAs

Higher eukaryotic chromosomes are organized into topologically constrained functional domains; however, the molecular mechanisms required to sustain these complex interphase chromatin structures are unknown. A stable matrix underpinning nuclear organization was hypothesized, but the idea was abandon...

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Autores principales: Nozawa, Ryu-Suke, Boteva, Lora, Soares, Dinesh C., Naughton, Catherine, Dun, Alison R., Buckle, Adam, Ramsahoye, Bernard, Bruton, Peter C., Saleeb, Rebecca S., Arnedo, Maria, Hill, Bill, Duncan, Rory R., Maciver, Sutherland K., Gilbert, Nick
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5473940/
https://www.ncbi.nlm.nih.gov/pubmed/28622508
http://dx.doi.org/10.1016/j.cell.2017.05.029
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author Nozawa, Ryu-Suke
Boteva, Lora
Soares, Dinesh C.
Naughton, Catherine
Dun, Alison R.
Buckle, Adam
Ramsahoye, Bernard
Bruton, Peter C.
Saleeb, Rebecca S.
Arnedo, Maria
Hill, Bill
Duncan, Rory R.
Maciver, Sutherland K.
Gilbert, Nick
author_facet Nozawa, Ryu-Suke
Boteva, Lora
Soares, Dinesh C.
Naughton, Catherine
Dun, Alison R.
Buckle, Adam
Ramsahoye, Bernard
Bruton, Peter C.
Saleeb, Rebecca S.
Arnedo, Maria
Hill, Bill
Duncan, Rory R.
Maciver, Sutherland K.
Gilbert, Nick
author_sort Nozawa, Ryu-Suke
collection PubMed
description Higher eukaryotic chromosomes are organized into topologically constrained functional domains; however, the molecular mechanisms required to sustain these complex interphase chromatin structures are unknown. A stable matrix underpinning nuclear organization was hypothesized, but the idea was abandoned as more dynamic models of chromatin behavior became prevalent. Here, we report that scaffold attachment factor A (SAF-A), originally identified as a structural nuclear protein, interacts with chromatin-associated RNAs (caRNAs) via its RGG domain to regulate human interphase chromatin structures in a transcription-dependent manner. Mechanistically, this is dependent on SAF-A’s AAA(+) ATPase domain, which mediates cycles of protein oligomerization with caRNAs, in response to ATP binding and hydrolysis. SAF-A oligomerization decompacts large-scale chromatin structure while SAF-A loss or monomerization promotes aberrant chromosome folding and accumulation of genome damage. Our results show that SAF-A and caRNAs form a dynamic, transcriptionally responsive chromatin mesh that organizes large-scale chromosome structures and protects the genome from instability.
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spelling pubmed-54739402017-06-26 SAF-A Regulates Interphase Chromosome Structure through Oligomerization with Chromatin-Associated RNAs Nozawa, Ryu-Suke Boteva, Lora Soares, Dinesh C. Naughton, Catherine Dun, Alison R. Buckle, Adam Ramsahoye, Bernard Bruton, Peter C. Saleeb, Rebecca S. Arnedo, Maria Hill, Bill Duncan, Rory R. Maciver, Sutherland K. Gilbert, Nick Cell Article Higher eukaryotic chromosomes are organized into topologically constrained functional domains; however, the molecular mechanisms required to sustain these complex interphase chromatin structures are unknown. A stable matrix underpinning nuclear organization was hypothesized, but the idea was abandoned as more dynamic models of chromatin behavior became prevalent. Here, we report that scaffold attachment factor A (SAF-A), originally identified as a structural nuclear protein, interacts with chromatin-associated RNAs (caRNAs) via its RGG domain to regulate human interphase chromatin structures in a transcription-dependent manner. Mechanistically, this is dependent on SAF-A’s AAA(+) ATPase domain, which mediates cycles of protein oligomerization with caRNAs, in response to ATP binding and hydrolysis. SAF-A oligomerization decompacts large-scale chromatin structure while SAF-A loss or monomerization promotes aberrant chromosome folding and accumulation of genome damage. Our results show that SAF-A and caRNAs form a dynamic, transcriptionally responsive chromatin mesh that organizes large-scale chromosome structures and protects the genome from instability. Cell Press 2017-06-15 /pmc/articles/PMC5473940/ /pubmed/28622508 http://dx.doi.org/10.1016/j.cell.2017.05.029 Text en © 2017 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Nozawa, Ryu-Suke
Boteva, Lora
Soares, Dinesh C.
Naughton, Catherine
Dun, Alison R.
Buckle, Adam
Ramsahoye, Bernard
Bruton, Peter C.
Saleeb, Rebecca S.
Arnedo, Maria
Hill, Bill
Duncan, Rory R.
Maciver, Sutherland K.
Gilbert, Nick
SAF-A Regulates Interphase Chromosome Structure through Oligomerization with Chromatin-Associated RNAs
title SAF-A Regulates Interphase Chromosome Structure through Oligomerization with Chromatin-Associated RNAs
title_full SAF-A Regulates Interphase Chromosome Structure through Oligomerization with Chromatin-Associated RNAs
title_fullStr SAF-A Regulates Interphase Chromosome Structure through Oligomerization with Chromatin-Associated RNAs
title_full_unstemmed SAF-A Regulates Interphase Chromosome Structure through Oligomerization with Chromatin-Associated RNAs
title_short SAF-A Regulates Interphase Chromosome Structure through Oligomerization with Chromatin-Associated RNAs
title_sort saf-a regulates interphase chromosome structure through oligomerization with chromatin-associated rnas
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5473940/
https://www.ncbi.nlm.nih.gov/pubmed/28622508
http://dx.doi.org/10.1016/j.cell.2017.05.029
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