A progeria mutation reveals functions for lamin A in nuclear assembly, architecture, and chromosome organization

Pekka Taimen, Katrin Pfleghaar, Takeshi Shimi, Dorothee Möller, Kfir Ben-Harush, Michael R. Erdos, Stephen A. Adam, Harald Herrmann, Ohad Medalia, Francis S. Collins, Anne E. Goldman, Robert D. Goldman

Research output: Contribution to journalArticlepeer-review

164 Scopus citations


Numerous mutations in the human A-type lamin gene (LMNA) cause the premature aging disease, progeria. Some of these are located in the α-helical central rod domain required for the polymerization of the nuclear lamins into higher order structures. Patient cells with a mutation in this domain, 433G>A (E145K) show severely lobulated nuclei, a separation of the A- and B-type lamins, alterations in pericentric heterochromatin, abnormally clustered centromeres, and mislocalized telomeres. The induction of lobulations and the clustering of centromeres originate during postmitotic nuclear assembly in daughter cells and this early G1 configuration of chromosomes is retained throughout interphase. In vitro analyses of E145K-lamin A show severe defects in the assembly of protofilaments into higher order lamin structures. The results show that this central rod domain mutation affects nuclear architecture in a fashion distinctly different from the changes found in the most common form of progeria caused by the expression of LAΔ50/ progerin. The study also emphasizes the importance of lamins in nuclear assembly and chromatin organization.

Original languageEnglish
Pages (from-to)20788-20793
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number49
StatePublished - 8 Dec 2009


  • Centromere
  • Chromatin
  • Rabl
  • Senescence
  • Telomere

ASJC Scopus subject areas

  • General


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