Resumen: 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. Idioma: Inglés DOI: 10.1016/j.cell.2017.05.029 Año: 2017 Publicado en: CELL 169, 7 (2017), 1214-1227 ISSN: 0092-8674 Factor impacto JCR: 31.398 (2017) Categ. JCR: CELL BIOLOGY rank: 3 / 190 = 0.016 (2017) - Q1 - T1 Categ. JCR: BIOCHEMISTRY & MOLECULAR BIOLOGY rank: 2 / 292 = 0.007 (2017) - Q1 - T1 Factor impacto SCIMAGO: 25.137 - Biochemistry, Genetics and Molecular Biology (miscellaneous) (Q1)