Functional Analysis of Interactions Between 53BP1, BRCA1 and p53
Abstract
53BP1 has been reported to interact with the central DNA-binding domain of the tumor suppressor p53 and to enhance p53-dependent transcription. The C-terminus of 53BP1 contains a tandem BRCT motif. This domain was first identified in the C-terminal region of BRCA1 and has since been found in several proteins involved in various aspects of cell cycle control, recombination and DNA repair. The interaction with p53 and sequence homology with BRCA1 raised the possibility that 53BP1 may be involved in the maintenance of genomic stability. Western blot and immunofluorescence studies showed that upon DNA damage 53BP1 becomes hyperphosphorylated and forms discrete nuclear foci at the sites of DNA lesions. Co-immunostaining analyses revealed that these foci co-localize with BRCA1 foci several hours after DNA damage. Furthermore, small amounts of 53BP1 can be Co-immunoprecipitated with BRCA1 after irradiation but not in untreated cells. Like BECA1, 53BP1 becomes phosphorylated by ATM in vivo following ionizing radiation. Both proteins were also found to localize to stalled replication forks in response to replicational stress. These findings indicate that 53BP1 is involved in the early response to genotoxic stress. Given its interactions with p53 and BRCA1 it is reasonable to predict that 53BP1 might also act as a tumor suppressor.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2002
- Accession Number
- ADA408225
Entities
People
- Irene M. Ward
- Junjie Chen
Organizations
- Mayo Clinic