title: Loss of A-type lamins and genomic instability.
abstract: Research performed in the last few years has revealed important roles for the spatial and temporal organization of the genome on genome function and integrity. A challenge in the field is to determine the molecular mechanisms involved in the organization of genome function. A-type lamins, key structural components of the nucleus, have been implicated in the maintenance of nuclear architecture and chromatin structure. Interestingly, alterations of A-type lamins lead to defects in DNA replication and repair as well as gene transcription and silencing. Elucidating the functions of these proteins is a topical subject since alterations of A-type lamins are associated with a variety of human diseases, ranging from muscular dystrophies and premature aging syndromes to cancer. Here, we discuss novels roles for A-type lamins in the maintenance of telomere structure, length and function as well as in the stabilization of a key DNA damage response factor. These studies support the notion that increased genomic instability due to defects in telomere biology and DNA repair contribute to the pathogenesis of lamin-related diseases.
authors.affiliation: Radiation and Cancer Biology Division, Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO, USA. sgonzalo@radonc.wustl.edu
authors.forename: Ignacio
authors.initials: I
authors.lastname: Gonzalez-Suarez
authors.forename: Abena B
authors.initials: AB
authors.lastname: Redwood
authors.forename: Susana
authors.initials: S
authors.lastname: Gonzalo
mesh_terms: D004249:DNA Damage; D004260:DNA Repair; D018390:Gene Targeting / Q000379:methods; D042822:Genomic Instability; D006801:Humans; D034904:Lamin Type A / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016615:Telomere / Q000378:metabolism / Q000502:physiology
chemical_list: D034904:Lamin Type A