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Related Concept Videos

DNA Helicases00:55

DNA Helicases

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DNA unwinding helicase enzymes are a type of motor protein. Motor proteins can translocate along filaments or polymers using energy generated from ATP hydrolysis. Helicases are involved in all the important cellular processes where DNA unwinding is required, such as DNA replication, repair, recombination, and transcription. They are present in all living organisms, but vary in their structure, function, and mechanism of action. For example, in prokaryotes, DnaB helicase binds and translocates...
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Separation of Sister Chromatids02:17

Separation of Sister Chromatids

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At the transition from prophase to metaphase, there is a reduction in cohesion along the chromosomal arms, resulting in the resolution of sister chromatids. However, residual cohesin connections remain to hold the sister chromatids together until the transition from metaphase to anaphase. The residual connection prevents any premature separation of sister chromatids, blocking the risks of aneuploidy within the daughter cells.
At the onset of anaphase, separase, a proteolytic enzyme, is...
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M-Cdk Drives Transition Into Mitosis02:15

M-Cdk Drives Transition Into Mitosis

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Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
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Anaphase Promoting Complex00:50

Anaphase Promoting Complex

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The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
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Condensins02:15

Condensins

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Condensins are large protein complexes that use ATP to fuel the assembly of chromosomes during mitosis. They transform the tangled, shapeless mass of post-interphase DNA into individualized chromosomes by compacting, organizing, and segregating chromosomal DNA.
The plant and animal cells contain two types of condensin complexes—condensin I and condensin II. Both complexes have five subunits: two SMC (Structural Maintenance of Chromosomes) subunits, a kleisin subunit, and two HEAT-repeat...
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DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

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In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
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Author Spotlight: Investigating the Motion Dynamics of the Eukaryotic Replisome Components at the Single-Molecule Level
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Structure of human Cdc45 and implications for CMG helicase function.

Aline C Simon1, Vincenzo Sannino2, Vincenzo Costanzo2

  • 1Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, UK.

Nature Communications
|May 19, 2016
PubMed
Summary

Human Cdc45 protein

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Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • Cell division cycle protein 45 (Cdc45) is essential for DNA replication as part of the CMG helicase.
  • The precise biochemical function of Cdc45 in DNA synthesis remains unclear.

Purpose of the Study:

  • To elucidate the molecular mechanism and structural basis of human Cdc45 function in eukaryotic DNA replication.

Main Methods:

  • X-ray crystallography (2.1-Å resolution) of human Cdc45.
  • Mutational analysis.
  • Integration with existing electron microscopy data.

Main Results:

  • The crystal structure reveals Cdc45's evolutionary link to bacterial RecJ nucleases.
  • Unexpected structural features, including domain interactions and helical insertions, were identified.
  • Mutational analysis confirmed Cdc45's role in associating with MCM and GINS for CMG helicase assembly.

Conclusions:

  • The study provides a molecular understanding of Cdc45's structure and its essential role in CMG helicase function.
  • These findings offer insights into the mechanism of eukaryotic DNA replication and genome duplication.