| First Author | Gonzalez-Suarez I | Year | 2009 |
| Journal | EMBO J | Volume | 28 |
| Issue | 16 | Pages | 2414-27 |
| PubMed ID | 19629036 | Mgi Jnum | J:152006 |
| Mgi Id | MGI:4355768 | Doi | 10.1038/emboj.2009.196 |
| Citation | Gonzalez-Suarez I, et al. (2009) Novel roles for A-type lamins in telomere biology and the DNA damage response pathway. EMBO J 28(16):2414-27 |
| abstractText | 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. |
