Novel roles for A-type lamins in telomere biology and the DNA damage response pathway.
EMBO J
; 28(16): 2414-27, 2009 Aug 19.
Article
em En
| MEDLINE
| ID: mdl-19629036
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Telômero
/
Lamina Tipo A
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Reparo do DNA
Limite:
Animals
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article