Conserved BRCT regions of TopBP1 and of the tumor suppressor BRCA1 bind strand breaks and termini of DNA.
The BRCT region, the carboxyl-terminus of BRCA1 (the breast cancer susceptibility gene 1 product), is a ubiquitous region homologous to regions in DNA repair enzymes and cell cycle regulators. We showed that the BRCT regions bound DNA fragments, using the TopBP1 protein (topoisomerase II binding protein 1), with eight BRCTs as a model protein. The bindings were independent of DNA sequences, forms of DNA termini and energy. The BRCT-DNA complex showed resistance to an exonuclease, indicating that BRCT bound DNA breaks. The BRCTs also bound DNA nicks, suggesting that BRCTs play an important role in detection of both single- and double-strand DNA breaks or ends. On the other hand, BRCTs did not bind circular intact DNA. BRCTs of BRCA1 also bound DNA termini. Since some BRCTs are unique general elements in some tumor suppressions, these findings will reveal novel aspects of the tumor suppression mechanism.
Yamane
K
K
Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
Tsuruo
T
T
D019313:BRCA1 Protein / Q000737:chemistry / Q000378:metabolism*; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D002453:Cell Cycle; D016384:Consensus Sequence; D004247:DNA / Q000378:metabolism / Q000528:radiation effects; D004249:DNA Damage; D004260:DNA Repair; D004270:DNA, Circular / Q000378:metabolism; D004277:DNA, Single-Stranded / Q000378:metabolism; D004268:DNA-Binding Proteins; D019143:Evolution, Molecular; D006801:Humans; D009687:Nuclear Proteins; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D014466:Ultraviolet Rays
D019313:BRCA1 Protein; D002352:Carrier Proteins; D004270:DNA, Circular; D004277:DNA, Single-Stranded; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D016376:Oligonucleotides, Antisense; D011993:Recombinant Fusion Proteins; C110513:TOPBP1 protein, human; D004247:DNA