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Related Concept Videos

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...
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...
Long-patch Base Excision Repair01:02

Long-patch Base Excision Repair

Since the discovery of the two BER pathways, there has been a debate about how a cell chooses one pathway over the other and the factors determining this selection. Numerous in vitro experiments have pointed out multiple determinants for the sub-pathway selection. These are:
Mismatch Repair01:20

Mismatch Repair

Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...

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Analysis of Nonhomologous End Joining and Homologous Recombination Efficiency in HEK-293T Cells Using GFP-Based Reporter Systems
09:29

Analysis of Nonhomologous End Joining and Homologous Recombination Efficiency in HEK-293T Cells Using GFP-Based Reporter Systems

Published on: February 2, 2024

Modeling non-homologous end joining.

Yongfeng Li1, Francis A Cucinotta

  • 1USRA, Division of Space Life Sciences, Houston, TX 77058, United States. li@dsls.usra.edu

Journal of Theoretical Biology
|June 4, 2011
PubMed
Summary
This summary is machine-generated.

Non-homologous end joining (NHEJ) repairs DNA double-strand breaks. Mathematical modeling shows that if a DNA-PKcs-independent pathway exists, both classical and new NHEJ models effectively repair DNA when sufficient proteins are present.

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Detection of Homologous Recombination Intermediates via Proximity Ligation and Quantitative PCR in Saccharomyces cerevisiae
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Detection of Homologous Recombination Intermediates via Proximity Ligation and Quantitative PCR in Saccharomyces cerevisiae
07:55

Detection of Homologous Recombination Intermediates via Proximity Ligation and Quantitative PCR in Saccharomyces cerevisiae

Published on: September 11, 2022

Area of Science:

  • Molecular Biology
  • Biochemistry
  • Genetics

Background:

  • Non-homologous end joining (NHEJ) is a critical DNA repair pathway for double-strand breaks (DSBs).
  • Key proteins like Ku, DNA-PKcs, Artemis, XRCC4/Ligase IV, and XLF orchestrate DNA damage detection, end processing, and ligation in NHEJ.
  • The classical NHEJ model posits a sequential recruitment of proteins, with DNA-PKcs binding first to Ku-bound DNA.

Purpose of the Study:

  • To theoretically investigate the impact of protein recruitment order on NHEJ efficiency.
  • To analyze the implications of a potential DNA-PKcs-independent DSB repair pathway.
  • To compare the classical sequential NHEJ model with a proposed two-phase model.

Main Methods:

  • Development of a mathematical model representing NHEJ as a biochemical reaction network.
  • Application of stability and related analyses to the mathematical model.
  • Theoretical demonstration of model behavior under varying conditions.

Main Results:

  • The study demonstrates that the classical sequential NHEJ model and a new two-phase model are theoretically indistinguishable.
  • This indistinguishability holds true when a DSB repair pathway independent of DNA-PKcs exists.
  • Thorough DSB repair is achievable in both models if adequate repair proteins are available.

Conclusions:

  • The precise order of protein recruitment in NHEJ may not be critical for complete DNA repair.
  • The existence of alternative, DNA-PKcs-independent repair mechanisms influences the overall model dynamics.
  • Sufficient protein availability is a key factor for effective DSB repair, regardless of the specific NHEJ model.