Distinct spatiotemporal dynamics of mammalian checkpoint regulators induced by DNA damage

摘要: Cell cycle checkpoints are signal transduction pathways activated after DNA damage to protect genomic integrity. Dynamic spatiotemporal coordination is a vital, but poorly understood aspect, of these checkpoints. Here, we provide evidence for strikingly different behaviour Chk2 versus Nbs1, key mediators the ataxia-telangiecatesia-mutated (ATM)-controlled checkpoint induced by double-strand breaks (DSBs). In live human cells with DSBs restricted small sub-nuclear areas, Nbs1 was rapidly recruited damaged regions and underwent dynamic exchange in close vicinity DSB sites. contrast, continued move throughout entire nucleus, irrespective including DSB-free areas. Although phosphorylation ATM occurred exclusively at sites, forced immobilization spatially restricted, DSB-containing nuclear areas impaired its stimulating effect on p53-dependent transcription. These results unravel nature interaction lesions identify as candidate transmitter signal, allowing coordinated pan-nuclear response focal damage.