Phosphorylation and Rapid Relocalization of 53BP1 to Nuclear Foci upon DNA Damage
AUTOR(ES)
Anderson, Lindsay
FONTE
American Society for Microbiology
RESUMO
53BP1 is a human BRCT protein that was originally identified as a p53-interacting protein by the Saccharomyces cerevisiae two-hybrid screen. Although the carboxyl-terminal BRCT domain shows similarity to Crb2, a DNA damage checkpoint protein in fission yeast, there is no evidence so far that implicates 53BP1 in the checkpoint. We have identified a Xenopus homologue of 53BP1 (XL53BP1). XL53BP1 is associated with chromatin and, in some cells, localized to a few large foci under normal conditions. Gamma-ray irradiation induces increased numbers of the nuclear foci in a dose-dependent manner. The damage-induced 53BP1 foci appear rapidly (in 30 min) after irradiation, and de novo protein synthesis is not required for this response. In human cells, 53BP1 foci colocalize with Mrel1 foci at later stages of the postirradiation period. XL53BP1 is hyperphosphorylated after X-ray irradiation, and inhibitors of ATM-related kinases delay the relocalization and reduce the phosphorylation of XL53BP1 in response to X-irradiation. In AT cells, which lack ATM kinase, the irradiation-induced responses of 53BP1 are similarly affected. These results suggest a role for 53BP1 in the DNA damage response and/or checkpoint control which may involve signaling of damage to p53.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=86718Documentos Relacionados
- PTIP Regulates 53BP1 and SMC1 at the DNA Damage Sites*
- hSnm1 Colocalizes and Physically Associates with 53BP1 before and after DNA Damage
- p53 Binding Protein 53BP1 Is Required for DNA Damage Responses and Tumor Suppression in Mice
- Crystal structure of human 53BP1 BRCT domains bound to p53 tumour suppressor
- Structure of the 53BP1 BRCT region bound to p53 and its comparison to the Brca1 BRCT structure