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Related Concept Videos

Anaphase Promoting Complex00:50

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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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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.
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Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
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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.
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Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay
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APC/C and SCF(cyclin F) Constitute a Reciprocal Feedback Circuit Controlling S-Phase Entry.

Rajarshi Choudhury1, Thomas Bonacci1, Anthony Arceci1

  • 1Lineberger Comprehensive Cancer Center and Department of Pharmacology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

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|September 23, 2016
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Summary
This summary is machine-generated.

The anaphase promoting complex/cyclosome (APC/C) and SCF ubiquitin ligases form a feedback loop. This circuit regulates cyclin F and Cdh1 degradation, controlling cell-cycle progression and genome integrity.

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • The anaphase promoting complex/cyclosome (APC/C) is a key ubiquitin ligase regulating the cell cycle.
  • APC/C, when bound to Cdh1, restricts S-phase entry and maintains genome integrity during G1 phase.

Purpose of the Study:

  • To elucidate a reciprocal feedback circuit between the APC/C and the SCF ubiquitin ligase.
  • To investigate the roles of cyclin F and Cdh1 in cell-cycle control.

Main Methods:

  • Investigated the degradation of cyclin F by APC/C.
  • Determined if Cdh1 is a substrate of SCF(cyclin F).
  • Assessed the impact of cyclin F loss on Cdh1 degradation and S-phase entry.

Main Results:

  • The APC/C targets cyclin F, an F-box protein and SCF substrate, for degradation.
  • Cdh1 is degraded by SCF(cyclin F).
  • Loss of cyclin F inhibits Cdh1 degradation, delaying S-phase entry, which is rescued by Cdh1 removal.

Conclusions:

  • A double-negative feedback loop between APC/C and SCF(cyclin F) governs the degradation of cyclin F and Cdh1.
  • This coordinated degradation is crucial for cell-cycle control and potentially other oscillating biological systems.