Induction of DNA replication-mediated double strand breaks by psoralen DNA interstrand cross-links

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69 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)5250-5254
Number of pages5
JournalJournal of Biological Chemistry
Volume278
Issue number7
DOIs
StatePublished - Feb 14 2003

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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