PMID- 10498869 OWN - NLM STAT- MEDLINE DCOM- 19991021 LR - 20071115 IS - 0950-9232 (Print) IS - 0950-9232 (Linking) VI - 18 IP - 37 DP - 1999 Sep 16 TI - Conserved BRCT regions of TopBP1 and of the tumor suppressor BRCA1 bind strand breaks and termini of DNA. PG - 5194-203 AB - 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. FAU - Yamane, K AU - Yamane K AD - Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan. FAU - Tsuruo, T AU - Tsuruo T LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Oncogene JT - Oncogene JID - 8711562 RN - 0 (BRCA1 Protein) RN - 0 (Carrier Proteins) RN - 0 (DNA, Circular) RN - 0 (DNA, Single-Stranded) RN - 0 (DNA-Binding Proteins) RN - 0 (Nuclear Proteins) RN - 0 (Oligonucleotides, Antisense) RN - 0 (Recombinant Fusion Proteins) RN - 0 (TOPBP1 protein, human) RN - 9007-49-2 (DNA) SB - IM MH - BRCA1 Protein/chemistry/*metabolism MH - Carrier Proteins/chemistry/*metabolism MH - Cell Cycle MH - Consensus Sequence MH - DNA/metabolism/radiation effects MH - DNA Damage MH - DNA Repair MH - DNA, Circular/metabolism MH - DNA, Single-Stranded/metabolism MH - DNA-Binding Proteins MH - Evolution, Molecular MH - Humans MH - Nuclear Proteins MH - Oligonucleotides, Antisense/pharmacology MH - Protein Binding MH - Recombinant Fusion Proteins/metabolism MH - Structure-Activity Relationship MH - Substrate Specificity MH - Ultraviolet Rays EDAT- 1999/09/28 00:00 MHDA- 1999/09/28 00:01 CRDT- 1999/09/28 00:00 PHST- 1999/09/28 00:00 [pubmed] PHST- 1999/09/28 00:01 [medline] PHST- 1999/09/28 00:00 [entrez] AID - 10.1038/sj.onc.1202922 [doi] PST - ppublish SO - Oncogene. 1999 Sep 16;18(37):5194-203. doi: 10.1038/sj.onc.1202922.