Premium
Novel roles for A‐type lamins in telomere biology and the DNA damage response pathway
Author(s) -
GonzalezSuarez Ignacio,
Redwood Abena B,
Perkins Stephanie M,
Vermolen Bart,
Lichtensztejin Daniel,
Grotsky David A,
MorgadoPalacin Lucia,
Gapud Eric J,
Sleckman Barry P,
Sullivan Teresa,
Sage Julien,
Stewart Colin L,
Mai Sabine,
Gonzalo Susana
Publication year - 2009
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2009.196
Subject(s) - lamin , biology , lmna , genome instability , telomere , nuclear lamina , heterochromatin , microbiology and biotechnology , premature aging , dna repair , dna damage , genetics , progeria , intermediate filament , mutation , chromatin , nuclear protein , gene , dna , cytoskeleton , cell , transcription factor
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.