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

Nozawa, R.S. ; Boteva, L. ; Soares, D.C. ; Naughton, C. ; Dun, A. ; Buckle, A. ; Ramsahoye, B. ; Bruton, P.C. ; Saleeb, R.S. ; Arnedo, M. ; Hill, B. ; Duncan, R.R. ; Maciver, S.K. ; Gilbert, N.

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)

Tipo y forma: Artículo (Versión definitiva)