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Related Concept Videos

Restarting Stalled Replication Forks02:37

Restarting Stalled Replication Forks

DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart, a...
Genome Copying Errors02:46

Genome Copying Errors

DNA replication is a well-evolved process that copies millions of base pairs with high fidelity during each cell division. Occasionally a wrong base or a long stretch of wrong bases may get added to the daughter strands. If the errors are left unchecked, cells might accumulate several mutations that might endanger their  survival. Therefore, the copying errors are checked and repaired at three levels.
Homologous Recombination02:31

Homologous Recombination

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...
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...
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...
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Gene Conversion

Other than maintaining genome stability via DNA repair, homologous recombination plays an important role in diversifying the genome. In fact, the recombination of sequences forms the molecular basis of genomic evolution. Random and non-random permutations of genomic sequences create a library of new amalgamated sequences. These newly formed genomes can determine the fitness and survival of cells. In bacteria, homologous and non-homologous types of recombination lead to the evolution of new...

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Updated: Jun 21, 2026

Using Next Generation Sequencing to Identify Mutations Associated with Repair of a CAS9-induced Double Strand Break Near the CD4 Promoter
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Using Next Generation Sequencing to Identify Mutations Associated with Repair of a CAS9-induced Double Strand Break Near the CD4 Promoter

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Specific pathways prevent duplication-mediated genome rearrangements.

Christopher D Putnam1, Tikvah K Hayes, Richard D Kolodner

  • 1Ludwig Institute for Cancer Research, Department of Medicine, University of California School of Medicine, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0669, USA.

Nature
|July 31, 2009
PubMed
Summary
This summary is machine-generated.

Certain yeast chromosome regions prone to duplication can cause genome instability. Specific genes and pathways suppress these rearrangements, preventing widespread genomic instability in cells with repetitive DNA sequences.

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Area of Science:

  • Genetics
  • Molecular Biology
  • Yeast Genetics

Background:

  • Eukaryotic genomes contain numerous divergent repeated sequences.
  • Understanding the mechanisms of genome instability is crucial for preventing diseases associated with genetic mutations.

Purpose of the Study:

  • To investigate the role of specific chromosome regions in Saccharomyces cerevisiae in the formation of gross chromosomal rearrangements (GCRs).
  • To identify genes and pathways involved in suppressing GCRs mediated by homologous recombination in repetitive DNA regions.

Main Methods:

  • Analysis of the left arm of Saccharomyces cerevisiae chromosome V.
  • Investigating the HXT13-DSF1 region for its propensity to form duplications and GCRs.
  • Assessing the role of various genes (SGS1, TOP3, SRS2, RAD6, SLX1, SLX4, SLX5, MSH2, MSH6, RAD10) and the DNA replication stress checkpoint (MRC1, TOF1) in suppressing GCRs.

Main Results:

  • The HXT13-DSF1 region, containing divergent homology similar to mammalian segmental duplications, was identified as 'at risk' for duplication-mediated GCRs.
  • Numerous genes and pathways were found to be specifically involved in suppressing these GCRs, differing from those suppressing single-copy sequence-mediated GCRs.

Conclusions:

  • Mechanisms for GCR formation and suppression differ between repetitive and single-copy DNA regions.
  • These findings explain how eukaryotic cells prevent extensive genome instability despite containing numerous divergent repeated sequences.