Oxydative stress alters nuclear shape through lamins dysregulation: a route to senescence.
Progeroid phenotypes are mainly encountered in 2 types of syndromes: in laminopathies, which are characterized by nuclear shape abnormalities due to lamin A alteration, and in DNA damage response defect syndromes. Because lamin A dysregulation leads to DNA damages, it has been proposed that senescence occurs in both types of syndromes through the accumulation of damages. We recently showed that elevated oxidative stress is responsible for lamin B1 accumulation, nuclear shape alteration and senescence in the DDR syndrome, ataxia telangiectasia (A-T). Interestingly, overexpression of lamin B1 in wild type cells is sufficient to induce senescence without the induction of DNA damages. Here, we will discuss the importance of controlling the lamins level in order for maintenance nuclear architecture and we will comment the relationships of lamins with other senescence mechanisms. Finally, we will describe emerging data reporting redox control by lamins, leading us to propose a general mechanism by which reactive oxygen species can induce senescence through lamin dysregulation and NSA.
Institut de Radiobiologie Cellulaire et Moléculaire, Laboratoire Réparation et Vieillissement, Fontenay-aux-Roses, France.
Aurélia
A
Barascu
Catherine
C
Le Chalony
Gaëlle
G
Pennarun
Diane
D
Genet
Nancy
N
Zaarour
Pascale
P
Bertrand
D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D053144:Cell Nucleus Shape; D016922:Cellular Senescence; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D034904:Lamin Type A / Q000378:metabolism*; D034921:Lamin Type B / Q000378:metabolism*; D051379:Mice; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011371:Progeria / Q000378:metabolism / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D016615:Telomere / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D034904:Lamin Type A; D034921:Lamin Type B; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; C576325:Atm protein, mouse; D017346:Protein Serine-Threonine Kinases