Duplications between direct repeats stabilized by DNA secondary structure occur preferentially in the leading strand during DNA replication

Vera Hashem, Richard R. Sinden

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

To ascertain a leading or lagging strand preference for duplication mutations, several short DNA sequences, i.e. mutation inserts, were designed that should demonstrate an asymmetric propensity for duplication mutations in the two complementary DNA strands during replication. The design of the mutation insert involved a 7-bp quasi inverted repeat that forms a remarkably stable hairpin in one DNA strand, but not the other. The inverted repeat is asymmetrically placed between flanking direct repeats. This sequence was cloned into a modified chloramphenicol acetyltransferase (CAT) gene containing a -1 frameshift mutation. Duplication of the mutation insert restores the reading frame of the CAT gene resulting in a chloramphenicol resistant phenotype. The mutation insert showed greater than a 200-fold preference for duplication mutations during leading strand, compared with lagging strand, replication. This result suggests that misalignment stabilized by DNA secondary structure, leading to duplication between direct repeats, occurred preferentially during leading strand synthesis.

Original languageEnglish (US)
Pages (from-to)215-226
Number of pages12
JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Volume570
Issue number2
DOIs
StatePublished - Mar 1 2005

Keywords

  • DNA instability
  • DNA replication
  • DNA secondary structure
  • Duplication mutation
  • Genome instability
  • Misalignment
  • Primer template misalignment
  • Repeat instability

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Health, Toxicology and Mutagenesis

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