DNA structure-induced genomic instability in vivo

Guliang Wang, Steve Carbajal, Jan Vijg, John DiGiovanni, Karen M. Vasquez

Research output: Contribution to journalArticle

59 Scopus citations

Abstract

Noncanonical DNA structures are postulated to be responsible for some breakpoint hotspots that occur frequently in cancers. We developed a novel mouse model system using the naturally occurring H-DNA structure that deviate from the familiar right-handed helical B form found at the breakage hotspot in the human c-MYC promoter and a Z-DNA-forming CG repeat to test this idea directly. Large-scale chromosomal deletions and/or translocations occurred in 5 (7.7%, 95% confidence interval [CI] = 3.7% to 12.8%) of the 65 mice carrying the H-DNA-forming sequences and in 7 (6.6%, 95% CI = 3.8% to 11.6%) of the 106 mice carrying the Z-DNA-forming sequences, but in 0 of the 63 control mice (P =. 042 and P =. 035, respectively, two-sided test). Thus, the DNA structure itself can introduce instability in a mammalian genome.

Original languageEnglish (US)
Pages (from-to)1815-1817
Number of pages3
JournalJournal of the National Cancer Institute
Volume100
Issue number24
DOIs
StatePublished - Dec 17 2008

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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