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

Ryu-Suke Nozawa, Lora Boteva, Dinesh C. Soares, Catherine Naughton, Alison R. Dun, Adam Buckle, Bernard Ramsahoye, Peter C. Bruton, Rebecca S. Saleeb, Maria Arnedo, Bill Hill, Rory R. Duncan, Sutherland K. Maciver, Nick Gilbert

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.

Original languageEnglish
Pages (from-to)1214-1227.e18
Number of pages22
Issue number7
Early online date15 Jun 2017
Publication statusPublished - 15 Jun 2017

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  • Journal Article


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