Remodelin

Remodelin markedly reduced the prevalence of misshapen nuclei in HGPS cells as well as in primary MRC5 fibroblasts aged in culture. In contrast, Remodelin had no effect on nonlaminopathic Werner syndrome cells. Remodelin can improve nuclear architecture, chromatin organization, and fitness of both human lamin A/C-depleted cells and HGPS-derived patient cells, and decrease markers of DNA damage in these cells. NAT10 was identified as the target of Remodelin that mediated nuclear shape rescue in laminopathic cells via microtubule reorganization by using a combination of chemical, cellular, and genetic approaches, acetyl-transferase protein. 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). Remodelin is a useful chemical tool to study how NAT10 affects nuclear architecture and suggest alternative strategies for treating laminopathies and aging.