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DNA Damage can Stall the Cell Cycle02:36

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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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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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Links between DNA Replication, Stem Cells and Cancer.

Alex Vassilev1, Melvin L DePamphilis2

  • 1Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bldg. 6A, Room 3A15, 6 Center Drive, Bethesda, MD 20892-2790, USA. vassilev@mail.nih.gov.

Genes
|January 27, 2017
PubMed
Summary

Cancer arises from DNA replication errors in stem cells or developmental errors involving pluripotent stem cells. Geminin protein is crucial for both, suggesting it as a target for eradicating cancer progenitor cells.

Keywords:
DNA re-replicationGeminincancer stem cellsembryonal carcinoma cellsembryonic stem cellsendoreplicationgerm cell neoplasiamitotic slippageteratocarcinomateratoma

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Area of Science:

  • Oncology
  • Developmental Biology
  • Genetics

Background:

  • Cancers are broadly classified into age-related types driven by DNA mutations in stem cells and developmental cancers like germ cell neoplasia.
  • Age-related cancers stem from accumulated mutations during stem cell proliferation, leading to genomic instability and drug resistance.
  • Germ cell neoplasia originates from misplaced pluripotent stem cells during embryonic development.

Purpose of the Study:

  • To explore the role of Geminin protein in both major cancer categories.
  • To identify Geminin as a potential therapeutic target for cancer progenitor cells.

Main Methods:

  • The study conceptually links DNA replication control in development with cancer mechanisms.
  • It highlights the dependence of pluripotent stem cells and cancer cells on Geminin.

Main Results:

  • Geminin protein prevents DNA damage-induced apoptosis triggered by excess DNA replication in both pluripotent stem cells and cancer cells.
  • A functional link is established between DNA replication control during development and germ cell neoplasia.

Conclusions:

  • Geminin is essential for preventing DNA damage-induced apoptosis in pluripotent stem cells and cancer cells.
  • Targeting Geminin offers a potential strategy for eradicating cancer progenitor cells, particularly in germ cell neoplasia.