doi: 10.1074/jbc.M212323200.
Epub 2002 Dec 8.
Induction of DNA replication-mediated double strand breaks by psoralen DNA interstrand cross-links
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- PMID: 12473662
- DOI: 10.1074/jbc.M212323200
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Induction of DNA replication-mediated double strand breaks by psoralen DNA interstrand cross-links
J Biol Chem.
.
Free article
Abstract
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.
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