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Title: Progerin reduces LAP2α-telomere association in Hutchinson-Gilford progeria
Authors: Chojnowski, Alexandre
Ong, Peh Fern
Wong, Esther S. M.
Lim, John S. Y.
Mutalif, Rafidah A.
Navasankari, Raju
Dutta, Bamaprasad
Yang, Henry
Liow, Yi Y.
Sze, Siu Kwan
Boudier, Thomas
Wright, Graham D.
Colman, Alan
Burke, Brian
Stewart, Colin L.
Dreesen, Oliver
Issue Date: 2015
Source: Chojnowski, A., Ong, P. F., Wong, E. S. M., Lim, J. S. Y., Mutalif, R. A., Navasankari, R., et al. (2015). Progerin reduces LAP2α-telomere association in Hutchinson-Gilford progeria. eLife, 4, e07759-.
Series/Report no.: eLife
Abstract: Hutchinson-Gilford progeria (HGPS) is a premature ageing syndrome caused by a mutation in LMNA, resulting in a truncated form of lamin A called progerin. Progerin triggers loss of the heterochromatic marker H3K27me3, and premature senescence, which is prevented by telomerase. However, the mechanism how progerin causes disease remains unclear. Here, we describe an inducible cellular system to model HGPS and find that LAP2α (lamina-associated polypeptide-α) interacts with lamin A, while its interaction with progerin is significantly reduced. Super-resolution microscopy revealed that over 50% of telomeres localize to the lamina and that LAP2α association with telomeres is impaired in HGPS. This impaired interaction is central to HGPS since increasing LAP2α levels rescues progerin-induced proliferation defects and loss of H3K27me3, whereas lowering LAP2 levels exacerbates progerin-induced defects. These findings provide novel insights into the pathophysiology underlying HGPS, and how the nuclear lamina regulates proliferation and chromatin organization.
ISSN: 2050-084X
DOI: 10.7554/eLife.07759
Schools: School of Biological Sciences 
Rights: © Copyright Chojnowski et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SBS Journal Articles

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