biostudies-literatureDworak NNIA NIH HHSNCI NIH HHSNational Institutes of HealthNIGMS NIH HHSe12851https://www.ebi.ac.uk/biostudies/studies/S-EPMC6351833biostudies-literatureUnknown18(1)The Ran GTPase regulates nuclear import and export by controlling the assembly state of transport complexes. This involves the direct action of RanGTP, which is generated in the nucleus by the chromatin-associated nucleotide exchange factor, RCC1. Ran interactions with RCC1 contribute to formation of a nuclear:cytoplasmic (N:C) Ran protein gradient in interphase cells. In previous work, we showed that the Ran protein gradient is disrupted in fibroblasts from Hutchinson-Gilford progeria syndrome (HGPS) patients. The Ran gradient disruption in these cells is caused by nuclear membrane association of a mutant form of Lamin A, which induces a global reduction in heterochromatin marked with Histone H3K9me3 and Histone H3K27me3. Here, we have tested the hypothesis that heterochromatin controls tAging cellA nuclear lamina-chromatin-Ran GTPase axis modulates nuclear import and DNA damage signaling.PMC6351833R01-AG040162R01 AG040162T32 GM008136T32 CA009109R15 GM128026Yang CSSnow CMakosa DChatterjee MJividen KPaschal BMSimke WCKelley JBDworak NJohnson IGfalseA nuclear lamina-chromatin-Ran GTPase axis modulates nuclear import and DNA damage signaling.The Ran GTPase regulates nuclear import and export by controlling the assembly state of transport complexes. This involves the direct action of RanGTP, which is generated in the nucleus by the chromatin-associated nucleotide exchange factor, RCC1. Ran interactions with RCC1 contribute to formation of a nuclear:cytoplasmic (N:C) Ran protein gradient in interphase cells. In previous work, we showed that the Ran protein gradient is disrupted in fibroblasts from Hutchinson-Gilford progeria syndrome (HGPS) patients. The Ran gradient disruption in these cells is caused by nuclear membrane association of a mutant form of Lamin A, which induces a global reduction in heterochromatin marked with Histone H3K9me3 and Histone H3K27me3. Here, we have tested the hypothesis that heterochromatin controls t2019-01-01T00:00:00Z2019 Feb2026-07-09T12:22:54.198Z2019-03-26T22:50:29ZS-EPMC63518333056583610.1111/acel.12851