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Quantitation and Analysis of the Formation of HO-Endonuclease Stimulated Chromosomal Translocations by Single-Strand Annealing in Saccharomyces cerevisiae
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Quantitation and Analysis of the Formation of HO-Endonuclease Stimulated Chromosomal Translocations by Single-Strand Annealing in Saccharomyces cerevisiae

Published on: September 23, 2011

Induction of chromosomal translocations in mouse and human cells using site-specific endonucleases

David M Weinstock1, Erika Brunet, Maria Jasin

  • 1Department of Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10065, USA.

Journal of the National Cancer Institute. Monographs
|July 24, 2008
PubMed

Insights

Reciprocal chromosomal translocations, crucial in cancer, can be induced and studied using targeted DNA double-strand breaks. This research reveals nonhomologous end-joining mediates translocations, offering insights into cancer development.

Area of Science:

  • Genetics
  • Molecular Biology
  • Cancer Research

Background:

  • Reciprocal chromosomal translocations are key events in tumor development.
  • Mechanisms underlying translocation formation remain largely unknown.
  • Understanding these mechanisms is vital for cancer research.

Purpose of the Study:

  • To review methods for inducing and recovering translocations between targeted DNA double-strand breaks (DSBs).
  • To investigate translocation formation in mammalian cells.
  • To compare translocation junctions with those found in human tumors.

Main Methods:

  • Induction of two targeted DNA double-strand breaks (DSBs) using site-specific endonucleases in mouse cells.
  • Analysis of translocation junctions and their associated DNA modifications.
  • Development of a novel approach to induce translocations in human cells.

Main Results:

  • Nonhomologous end-joining readily mediates translocations between two DSBs.
  • Translocation formation is less frequent than intrachromosomal repair of a single DSB.
  • Translocation junctions exhibit extensive modifications, differing from single DSB repair.

Conclusions:

  • Model systems for inducing translocations are valuable for studying chromosomal rearrangements.
  • Mammalian DNA repair and signaling factors play roles in translocation etiology.
  • Further research can elucidate the precise mechanisms of translocation formation in cancer.

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