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Priming DNA replication from triple helix oligonucleotides: possible threestranded DNA in DNA polymerases

Patrick P Lestienne1

  • 1U 1053 INSERM, Université Victor Segalen Bordeaux 2, 146 rue Léo Saignat, 33076 Bordeaux, France.

Molecular Biology International
|January 10, 2012
PubMed

Insights

Triple helix primers (THP) can initiate DNA replication by binding to homologous sequences. This novel DNA polymerase interaction may explain illegitimate replication events.

Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • Triple helix forming oligonucleotides (TFOs) typically bind DNA antiparallel to polypurine/polypyrimidine sequences.
  • Known functions of TFOs include inhibition of transcription and replication, and induction of mutations.

Purpose of the Study:

  • To investigate a novel property of TFOs in DNA replication initiation.
  • To analyze the role of skewed polypurine-rich sequences in DNA rearrangements and replication priming.

Main Methods:

  • Analysis of DNA breakpoints associated with DNA rearrangements.
  • Synthesis of polypurine-rich sequences capable of forming triple helices.
  • Testing the ability of synthesized sequences to prime DNA replication using various DNA polymerases.

Main Results:

  • Synthesized polypurine-rich sequences form triple helices and prime DNA replication.
  • G-rich Triple Helix Primers (THP) bind homologous strands in a parallel orientation, potentially via a RecA-like mechanism.
  • This priming activity is conserved across diverse DNA polymerases (phage, retroviral, bacterial, human).

Conclusions:

  • DNA polymerases can interact with three polynucleotide strands, not just two.
  • Triple helix primers may facilitate illegitimate replication initiation following single-strand breaks and annealing.
  • This mechanism offers a new perspective on DNA replication and genomic instability.

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