Induction of DNA replication-mediated double strand breaks by psoralen DNA interstrand cross-links.
The effect of DNA interstrand cross-links (cross-links) on DNA replication was examined with a cell-free SV40 origin-dependent DNA replication system. A defined template DNA with a single psoralen cross-link and the SV40 origin of replication was replicated by HeLa cell-free extract in the presence of SV40 large T antigen. The psoralen cross-link inhibited DNA replication by terminating chain elongation at 1-50 nucleotides before the cross-linked sites. The termination of DNA replication by the cross-links mediated the generation of double strand breaks near the cross-linked sites. These results are the first biochemical evidence of the generation of double strand breaks by DNA replication.
Bessho
Tadayoshi
T
Department of Molecular Medicine, Institute of Biotechnology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78245-3207, USA. besshot@uthscsa.edu
D003432:Cross-Linking Reagents / Q000494:pharmacology; D004249:DNA Damage / Q000187:drug effects / Q000235:genetics*; D004261:DNA Replication / Q000187:drug effects* / Q000235:genetics*; D004279:DNA, Viral / Q000187:drug effects / Q000235:genetics; D005363:Ficusin / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D013539:Simian virus 40
D003432:Cross-Linking Reagents; D004279:DNA, Viral; D005363:Ficusin