The BRCT regions of tumor suppressor BRCA1 and of XRCC1 show DNA end binding activity with a multimerizing feature.
The BRCT regions are two repeating structures in BRCA1 at the carboxyl-terminus and are ubiquitous in some proteins involved in cell cycle checkpoint and in DNA repair. Here, using electron microscopy, we show direct evidence that the BRCT regions of BRCA1 bound double-strand breaks of DNA. The BRCT regions could multimerize thus forming large protein particles. Smeared patterns of DNA fragments were consistently shown in the gel retardation assay. A single BRCT was sufficient for DNA binding. The smeared patterns were also observed in BRCTs of TopBP1, suggesting that multimerization may be an important feature of BRCTs. The recombinant second BRCT of XRCC1 (X-ray repair cross-complementing group 1), whose folding was determined by X-ray crystallography, also showed similar DNA end binding images. It is possible that some BRCTs are fundamental structures that detect DNA damages.
Yamane
K
K
Laboratory of Biomedical Research, Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo, 113-0032, Japan.
Katayama
E
E
Tsuruo
T
T
D000595:Amino Acid Sequence; D019313:BRCA1 Protein / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D001665:Binding Sites; D004247:DNA / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D008024:Ligands; D008854:Microscopy, Electron; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D000076105:X-ray Repair Cross Complementing Protein 1
D019313:BRCA1 Protein; D004268:DNA-Binding Proteins; D008024:Ligands; D011993:Recombinant Fusion Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; D004247:DNA