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

ABSTRACT: Numerous mutations in the human A-type lamin gene (LMNA) cause the premature aging disease, progeria. Some of these are located in the alpha-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 high

SUBMITTER: Taimen P 

PROVIDER: S-EPMC2779830 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature