title: The tandem BRCT domain of 53BP1 is not required for its repair function.
abstract: 53BP1 plays an important role in cellular response to DNA damage. It is thought to be the mammalian homologue of budding yeast Rad9 and/or fission yeast Crb2. Rad9/Crb2 are bona fide checkpoint proteins whose activation requires their corresponding C-terminal tandem BRCT (BRCA1 C-terminal) motifs, which mediate their oligomerization and phosphorylation at multiple sites following DNA damage. Here we show that the function of human 53BP1 similarly depends on its oligomerization and phosphorylation at multiple sites but in a BRCT domain-independent manner. Moreover, unlike its proposed yeast counterparts, human 53BP1 only has limited checkpoint functions but rather acts as an adaptor in the repair of DNA double strand breaks. This difference in function may reflect the higher complexity of the DNA damage response network in metazoa including the evolution of other BRCT domain-containing proteins that may have functions redundant or overlapping with those of 53BP1.
authors.affiliation: Department of Oncology Research, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA.
authors.forename: Irene
authors.initials: I
authors.lastname: Ward
authors.forename: Ja-Eun
authors.initials: JE
authors.lastname: Kim
authors.forename: Kay
authors.initials: K
authors.lastname: Minn
authors.forename: Claudia C
authors.initials: CC
authors.lastname: Chini
authors.forename: Georges
authors.initials: G
authors.lastname: Mer
authors.forename: Junjie
authors.initials: J
authors.lastname: Chen
mesh_terms: D002460:Cell Line; D004260:DNA Repair / Q000502:physiology*; D006801:Humans; D047468:Immunoprecipitation; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D016297:Mutagenesis, Site-Directed; D010750:Phosphoproteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D000071857:Tumor Suppressor p53-Binding Protein 1
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; C498301:TP53BP1 protein, human; D000071857:Tumor Suppressor p53-Binding Protein 1