Novel roles for A-type lamins in telomere biology and the DNA damage response pathway

Academic Article

Abstract

  • A-type lamins are intermediate filament proteins that provide a scaffold for protein complexes regulating nuclear structure and function. Mutations in the LMNA gene are linked to a variety of degenerative disorders termed laminopathies, whereas changes in the expression of lamins are associated with tumourigenesis. The molecular pathways affected by alterations of A-type lamins and how they contribute to disease are poorly understood. Here, we show that A-type lamins have a key role in the maintenance of telomere structure, length and function, and in the stabilization of 53BP1, a component of the DNA damage response (DDR) pathway. Loss of A-type lamins alters the nuclear distribution of telomeres and results in telomere shortening, defects in telomeric heterochromatin, and increased genomic instability. In addition, A-type lamins are necessary for the processing of dysfunctional telomeres by non-homologous end joining, putatively through stabilization of 53BP1. This study shows new functions for A-type lamins in the maintenance of genomic integrity, and suggests that alterations of telomere biology and defects in DDR contribute to the pathogenesis of lamin-related diseases. © 2009 European Molecular Biology Organization.
  • Authors

    Digital Object Identifier (doi)

    Author List

  • Gonzalez-Suarez I; Redwood AB; Perkins SM; Vermolen B; Lichtensztejin D; Grotsky DA; Morgado-Palacin L; Gapud EJ; Sleckman BP; Sullivan T
  • Start Page

  • 2414
  • End Page

  • 2427
  • Volume

  • 28
  • Issue

  • 16