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Related Concept Videos

Crossing Over01:30

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Crossing over is the exchange of genetic information between homologous chromosomes during prophase I of meiosis I. Genetic recombination gives rise to allelic diversity in the newly formed daughter cells. In humans, crossing over produces genetically distinct haploid egg and sperm cells that undergo fertilization to produce unique offspring. Before cell division starts, the germ cell’s chromosome(s) undergo duplication in the S phase of the cell cycle. As the cells enter prophase I,...
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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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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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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,...
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A functional eukaryotic chromosome must contain three elements: a centromere, telomeres, and numerous origins of replication.
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Related Experiment Video

Updated: Feb 26, 2026

Generation and Purification of Human INO80 Chromatin Remodeling Complexes and Subcomplexes
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Generation and Purification of Human INO80 Chromatin Remodeling Complexes and Subcomplexes

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Structural and Functional Insights into Human Re-initiation Complexes.

Melanie Weisser1, Tanja Schäfer1, Marc Leibundgut1

  • 1Department of Biology, Institute of Molecular Biology and Biophysics, Otto-Stern-Weg 5, ETH Zurich, CH-8093 Zurich, Switzerland.

Molecular Cell
|July 23, 2017
PubMed
Summary
This summary is machine-generated.

Ribosomes can restart translation on mRNA via re-initiation, a process crucial for cancer-related gene expression. Researchers elucidated the structure of key proteins, eukaryotic translation initiation factor 2D (eIF2D) and MCT-1/DENR, involved in this vital cellular mechanism.

Keywords:
DENRMCT-1eIF2Dinitiator tRNAligatinribosomal recyclingstart codon recognitiontranslation initiationtranslation re-initiationtranslation regulation

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Area of Science:

  • Molecular Biology
  • Structural Biology
  • Biochemistry

Background:

  • Ribosome re-initiation is a critical post-termination process controlling gene expression for many mammalian mRNAs.
  • This mechanism is particularly important in cancer, where dysregulated translation can drive tumorigenesis.
  • Key protein factors, eukaryotic translation initiation factor 2D (eIF2D) and the MCT-1/DENR complex, mediate ribosomal binding for re-initiation.

Purpose of the Study:

  • To determine the structural basis of ribosomal re-initiation.
  • To elucidate the mechanism by which eIF2D and MCT-1/DENR interact with the 40S ribosomal subunit and initiator tRNA.
  • To understand how these factors facilitate translation re-initiation on mRNA.

Main Methods:

  • Cryo-electron microscopy (cryo-EM) was used to determine high-resolution structures.
  • X-ray crystallography provided complementary structural insights.
  • Biochemical experiments validated the structural findings and functional roles.

Main Results:

  • The structures reveal eIF2D bound to the human 40S ribosomal subunit with initiator tRNA in the P-site on an mRNA start codon.
  • eIF2D utilizes three flexible RNA-binding domains to monitor codon-anticodon interactions and position the tRNA.
  • These findings demonstrate how eIF2D mimics the functions of canonical translation initiation factors.

Conclusions:

  • The determined structures provide unprecedented insight into the molecular mechanism of ribosome re-initiation.
  • eIF2D's unique modular structure enables it to facilitate translation re-initiation, a process vital for regulating gene expression.
  • Understanding this mechanism offers potential avenues for therapeutic interventions in cancers associated with aberrant translation control.