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The liver is an important organ in vertebrates that plays an essential role in metabolism. It is also responsible for storing and redistributing nutrients such as carbohydrates, fats, and vitamins in the body. Additionally, the liver releases bile salts which are critical for digesting food and eliminating toxic metabolites from the body.
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The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
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The cell cycle regulation directs how a cell proceeds from one phase to the next and begins mitosis. The cell cycle control system includes intracellular regulatory molecules and external triggers. They provide "stop" or "advance" signals and operate at specific cell cycle stages termed checkpoints to ensure that a particular process is completed before the cell advances to the next phase.
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The cell cycle is an organized set of events that leads the cell to divide into two daughter cells, each containing chromosomes identical to the parent cell. It is the cell cycle that leads to the formation of an entire organism from a single-cell zygote. Besides, cell division also functions in the renewal or repair of tissues in adult multicellular eukaryotes. For example, in the bone marrow, the stem cells divide to form new blood cells. Although essential for several functions, cell...
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Several external and internal factors influence the initiation and inhibition of cell division. For instance, the death of nearby cells or the release of human growth hormone (hGH) promotes cell division. In contrast, lack of hGH or crowding of cells can inhibit cell division.
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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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APCCdh1 controls cell cycle entry during liver regeneration.

Ranran Cheng1, Xin Liang1, Quancheng Zhao1

  • 1Anhui Medical University, Hefei 230032, China; State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 102206, China.

Experimental Cell Research
|March 22, 2017
PubMed
Summary

Cdh1 depletion in mice causes extended S phase and DNA damage during liver regeneration. However, Cdh1 is not essential for hepatocyte regeneration competence after partial hepatectomy.

Keywords:
Cdh1Liver regenerationReplication

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • The anaphase-promoting complex/cyclosome (APC/C) is an E3 ubiquitin ligase crucial for cell cycle control.
  • Cdh1 is an adaptor protein of APC/C, but its in vivo functions, particularly in liver regeneration, remain incompletely understood.

Purpose of the Study:

  • To investigate the role of Cdh1 in liver regeneration using a conditional knock-out mouse model.
  • To elucidate the impact of Cdh1 loss on cell cycle progression, DNA replication, and DNA damage response during liver regeneration.

Main Methods:

  • Generation of a conditional Cdh1 knock-out mouse model.
  • Analysis of liver regeneration following partial hepatectomy.
  • Assessment of cell cycle progression (S phase), cyclin D1 levels, and DNA damage response.

Main Results:

  • Loss of Cdh1 resulted in prolonged S phase progression, potentially mediated by cyclin D1 upregulation.
  • Increased DNA replication in Cdh1-depleted hepatocytes triggered an activated DNA damage response.
  • Despite cell cycle alterations, Cdh1-deficient mice showed no difference in final liver weight post-hepatectomy compared to controls.

Conclusions:

  • Cdh1 plays a role in regulating S phase duration and DNA replication during liver regeneration.
  • The DNA damage response is activated upon Cdh1 loss, indicating a link between cell cycle control and genomic integrity.
  • Hepatocytes retain their regenerative capacity even in the absence of Cdh1, suggesting it is not essential for the fundamental process of liver regeneration.