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Related Concept Videos

Nucleotide Excision Repair01:08

Nucleotide Excision Repair

Overview
Fixing Double-strand Breaks02:04

Fixing Double-strand Breaks

The double-stranded structure of DNA has two major advantages. First, it serves as a safe repository of genetic information where one strand serves as the back-up in case the other strand is damaged. Second, the double-helical structure can be wrapped around proteins called histones to form nucleosomes, which can then be tightly wound to form chromosomes. This way, DNA chains up to 2 inches long can be contained within microscopic structures in a cell. A double-stranded break not only damages...
Homologous Recombination02:31

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The basic reaction of homologous recombination (HR) involves two chromatids that contain DNA sequences sharing a significant stretch of identity. One of these sequences uses a strand from another as a template to synthesize DNA in an enzyme-catalyzed reaction. The final product is a novel amalgamation of the two substrates. To ensure an accurate recombination of sequences, HR is restricted to the S and G2 phases of the cell cycle. At these stages, the DNA has been replicated already and the...
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Conservative Site-specific Recombination and Phase Variation

Because the DNA segments are cut and reorganized in a direction-specific manner, site-specific recombination has emerged as an efficient genetic engineering technique. Flippase and Cyclization recombinases or Flp and Cre, respectively, are two members of the tyrosine recombinase family derived from bacteriophages, that are used to mediate site-specific DNA insertions, deletions, and targeted expression of proteins in mammalian cell lines.
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Related Experiment Video

Updated: May 12, 2026

Quantitation and Analysis of the Formation of HO-Endonuclease Stimulated Chromosomal Translocations by Single-Strand Annealing in Saccharomyces cerevisiae
09:40

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

Published on: September 23, 2011

Complex chromosomal rearrangements mediated by break-induced replication involve structure-selective endonucleases.

Benjamin Pardo1, Andrés Aguilera

  • 1Centro Andaluz de Biología Molecular y Medicina Regenerativa CABIMER, Universidad de Sevilla, Sevilla, Spain.

Plos Genetics
|October 17, 2012
PubMed
Summary

DNA double-strand break (DSB) repair in repetitive DNA can cause chromosomal rearrangements. Structure-selective endonucleases Mus81 and Yen1 promote break-induced replication (BIR), leading to non-reciprocal translocations and genomic instability.

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Area of Science:

  • Molecular Biology
  • Genetics
  • Cancer Research

Background:

  • DNA double-strand breaks (DSBs) in repetitive sequences can lead to chromosomal rearrangements.
  • Homologous recombination typically repairs DSBs using a donor template for genetic information transfer.
  • Break-induced replication (BIR) is a pathway that can occur when only one DSB end has homology, often resulting in non-reciprocal translocations (NRTs) common in cancers.

Purpose of the Study:

  • To investigate the role of structure-selective endonucleases (SSEs) in DSB repair pathways.
  • To elucidate the mechanisms by which BIR generates chromosomal translocations.
  • To identify the specific SSEs involved in promoting BIR and template switching.

Main Methods:

  • Development of a novel substrate for analyzing DSB-induced chromosomal translocations.
  • Experimental analysis of the function of Mus81, Yen1, and Slx4 in DSB repair and BIR.
  • Investigation of replication fork establishment and template switching during BIR.

Main Results:

  • Mus81 and Yen1 SSEs were found to promote BIR, leading to the formation of NRTs.
  • These SSEs are proposed to be recruited at the strand invasion intermediate to facilitate replication fork establishment for BIR completion.
  • Mus81, Yen1, and Slx4 were shown to promote template switching during BIR, contributing to complex rearrangements.

Conclusions:

  • SSEs, including Mus81 and Yen1, play a crucial role in multiple stages of the BIR pathway.
  • These SSEs contribute to genomic instability by facilitating the generation of complex chromosomal rearrangements during BIR.
  • The findings highlight the involvement of SSEs in cancer-associated chromosomal abnormalities.