Author response: Progerin reduces LAP2α-telomere association in Hutchinson-Gilford progeria

作者：Alexandre Chojnowski, Peh Fern Ong, Esther Wong, John SY Lim, Rafidah Mutalif, Raju Navasankari, Bamaprasad Dutta, Henry Yang, Yi Y Liow, Siu Kwan Sze, Thomas Boudier, Graham Wright, Alan Colman, Brian Burke, Colin L. Stewart, Oliver Dreesen · 年份：2015 · DOI：10.7554/elife.07759.019 · 被引用次数：3 · 研究领域：Nuclear Structure and Function、Mitochondrial Function and Pathology、Biotin and Related Studies

Hutchinson-Gilford Progeria Syndrome (HGPS) is a rare genetic disease in which individuals age prematurely. Newborns appear normal at birth, but start ageing rapidly when they are around a year old. Symptoms of the disease include stunted growth and joint stiffness, and individuals often die of heart failure during their teens. A mutated version of a protein called lamin A causes HGPS; this mutant is known as progerin. In cells that produce progerin, the ‘telomeres’ that protect the ends of chromosomes (the structures that contain most of the cell's DNA) from damage, are unusually short. Every time a cell divides, the telomeres get shorter. If they get too short, the DNA is damaged and the cell stops dividing and enters a state known as senescence. HGPS affects some of the tissues in the body more severely than others, and these tissues tend to produce high levels of progerin. By gradually raising the levels of progerin in human cells, Chojnowski et al. found that DNA damage and cell senescence only occur when the amount of progerin in a cell exceeds a particular threshold. Moreover, the expression of telomerase—a complex that can elongate telomeres—prevented progerin-induced DNA damage and premature senescence. To find out how progerin affects cells, Chojnowski et al. compared how lamin A and progerin interact with other proteins. This revealed that progerin interacts with a protein called LAP2α more weakly than lamin A. LAP2α normally associates with telomeres, but using su...