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Updated: Feb 25, 2026

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

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Multi-invasions Are Recombination Byproducts that Induce Chromosomal Rearrangements

Aurèle Piazza1, William Douglass Wright1, Wolf-Dietrich Heyer2

  • 1Department of Microbiology and Molecular Genetics, One Shields Avenue, University of California, Davis, Davis, CA 95616, USA.

Cell
|August 8, 2017
PubMed

Insights

A new DNA repair pathway called multi-invasion-induced rearrangement (MIR) can cause chromosome translocations. This process, driven by broken DNA ends invading intact chromosomes, can lead to further DNA damage and has implications for diseases.

Area of Science:

  • Genetics
  • Molecular Biology
  • Genomics

Background:

  • Chromosome structural variants arise from inaccurate DNA repair.
  • These variants can drive evolution and cause diseases.

Purpose of the Study:

  • To describe a novel DNA rearrangement mechanism.
  • To elucidate the molecular players and conditions influencing this mechanism.

Main Methods:

  • Investigated DNA repair intermediates using genetic and biochemical approaches.
  • Analyzed the roles of specific nucleases and recombination factors in the process.
  • Studied the consequences of the rearrangement on chromosome integrity.

Main Results:

  • Identified a new mechanism, multi-invasion-induced rearrangement (MIR), where a single broken DNA end invades two separate intact chromosomes.
  • Demonstrated that MIR is independent of homology between donor chromosomes but requires specific structure-selective endonucleases (Mus81-Mms4, Slx1-Slx4, Yen1).
  • Showed that MIR is inhibited by factors that resolve recombination intermediates (Rad1-Rad10, Sgs1-Top3-Rmi1, Srs2, Mph1) and can lead to secondary chromosome breaks and further rearrangements.

Conclusions:

  • MIR is a novel pathway for generating translocations and complex genomic rearrangements.
  • The mechanism highlights the intricate interplay of DNA repair enzymes in maintaining genome stability.
  • MIR has significant implications for understanding the etiology of various human pathologies associated with chromosomal abnormalities.
Keywords:
D-loopchromothripsisendonucleasegenomic instabilityhelicasehomologous recombinationhomology searchmulti-invasiontranslocation

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