title: Nurturing the genome: A-type lamins preserve genomic stability.
abstract: A-type lamins provide a scaffold for tethering chromatin and protein complexes regulating nuclear structure and function. Interest in lamins increased after mutations in the LMNA gene were found to be associated with a variety of human disorders termed laminopathies. These include muscular dystrophy, cardiomyopathy, lipodystrophy, peripheral neuropathy and premature aging syndromes such as progeria. In addition, altered expression of A-type lamins is emerging as a contributing factor to tumorigenesis. How different alterations in a gene that is ubiquitously expressed can cause such an array of systemic as well as tissue specific diseases remains an enigma. Several lines of evidence indicate that mutant forms of A-type lamins impact on genome function and integrity. A current model suggests that genomic instability plays a major part in the pathophysiology of some lamin-related diseases. However, this model remains to be fully investigated. Here we discuss recent studies revealing novel functions for A-type lamins in the maintenance of telomeres and in the DNA damage response (DDR) pathway. These findings have shed some light onto the putative molecular mechanisms by which alterations in A-type lamins induce genomic instability and contribute to disease.
authors.affiliation: Radiation and Cancer Biology Division, Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Gonzalez-Suarez
authors.forename: Susana
authors.initials: S
authors.lastname: Gonzalo
mesh_terms: D000818:Animals; D004249:DNA Damage / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D016678:Genome / Q000235:genetics*; D042822:Genomic Instability; D006801:Humans; D034904:Lamin Type A / Q000172:deficiency / Q000378:metabolism*; D016615:Telomere / Q000235:genetics / Q000378:metabolism
chemical_list: D034904:Lamin Type A