期刊
SCIENCE
卷 344, 期 6183, 页码 527-532出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1252651
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资金
- Cancer Research UK [C6/A11224]
- European Research Council
- European Community [HEALTH-F2-2010-259893]
- CRUK [C6946/A14492]
- Wellcome Trust [WT092096]
- University of Cambridge, UK
- European Molecular Biology Organization (EMBO) long-term fellowship [ALTF 834-2011]
- Medical Research Council, UK [MR/L019116/1]
- EMBO [ALTF 93-2010]
- CRUK
- CNRS
- European Research Council grant DDREAM
- Cancer Research UK [11224] Funding Source: researchfish
- Medical Research Council [MR/L019116/1] Funding Source: researchfish
- MRC [MR/L019116/1] Funding Source: UKRI
Down-regulation and mutations of the nuclear-architecture proteins lamin A and C cause misshapen nuclei and altered chromatin organization associated with cancer and laminopathies, including the premature-aging disease Hutchinson-Gilford progeria syndrome (HGPS). Here, we identified the small molecule Remodelin that improved nuclear architecture, chromatin organization, and fitness of both human lamin A/C-depleted cells and HGPS-derived patient cells and decreased markers of DNA damage in these cells. Using a combination of chemical, cellular, and genetic approaches, we identified the acetyl-transferase protein NAT10 as the target of Remodelin that mediated nuclear shape rescue in laminopathic cells via microtubule reorganization. These findings provide insights into how NAT10 affects nuclear architecture and suggest alternative strategies for treating laminopathies and aging.
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