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Related Concept Videos

Fixing Double-strand Breaks02:04

Fixing Double-strand Breaks

The double-stranded structure of DNA has two major advantages. First, it serves as a safe repository of genetic information where one strand serves as the back-up in case the other strand is damaged. Second, the double-helical structure can be wrapped around proteins called histones to form nucleosomes, which can then be tightly wound to form chromosomes. This way, DNA chains up to 2 inches long can be contained within microscopic structures in a cell. A double-stranded break not only damages...
Fixing Double-strand Breaks02:04

Fixing Double-strand Breaks

The double-stranded structure of DNA has two major advantages. First, it serves as a safe repository of genetic information where one strand serves as the back-up in case the other strand is damaged. Second, the double-helical structure can be wrapped around proteins called histones to form nucleosomes, which can then be tightly wound to form chromosomes. This way, DNA chains up to 2 inches long can be contained within microscopic structures in a cell. A double-stranded break not only damages...
Homologous Recombination02:31

Homologous Recombination

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...
Homologous Recombination02:31

Homologous Recombination

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...
DNA Damage Can Stall the Cell Cycle02:36

DNA Damage Can Stall the Cell Cycle

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...
DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

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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Visualization of DNA Repair Proteins Interaction by Immunofluorescence
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Published on: June 26, 2020

Polycomb repressive complex 2 contributes to DNA double-strand break repair.

Stuart Campbell1, Ismail Hassan Ismail, Leah C Young

  • 1Department of Oncology, Faculty of Medicine and Dentistry, University of Alberta, Cross Cancer Institute, Edmonton, Alberta, Canada.

Cell Cycle (Georgetown, Tex.)
|August 3, 2013
PubMed
Summary

Enhancer of Zeste homolog 2 (EZH2) and Polycomb Repressive Complex 2 (PRC2) are recruited to DNA damage sites, impacting double-strand break repair and cancer cell sensitivity to radiation therapy.

Keywords:
DNA damagePARPchromatinepigeneticspolycomb group proteins

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Area of Science:

  • Epigenetics
  • Molecular Biology
  • Cancer Research

Background:

  • Enhancer of Zeste homolog 2 (EZH2) is a Polycomb protein involved in cancer cell proliferation and invasion.
  • The role of EZH2 in the DNA damage response remains largely uncharacterized.

Purpose of the Study:

  • To investigate the role of EZH2 and Polycomb Repressive Complex 2 (PRC2) in DNA damage response pathways.
  • To determine if EZH2 influences cancer cell sensitivity to DNA damaging agents.

Main Methods:

  • Recruitment of PRC2 to DNA damage sites was assessed.
  • The dependence of PRC2 recruitment on H2AX and PI-3 kinases (ATM, DNA-PKcs) was evaluated.
  • The requirement of PARP activity for PRC2 retention at damage sites was established.
  • The effect of EZH2 depletion on double-strand break (DSB) repair efficiency and gamma-irradiation sensitivity was analyzed.

Main Results:

  • PRC2 is recruited to DNA damage sites independently of H2AX and ATM/DNA-PKcs.
  • PARP activity is essential for retaining PRC2 at sites of DNA damage.
  • Depletion of EZH2 impairs DSB repair and increases sensitivity to gamma-irradiation.

Conclusions:

  • PRC2 plays a critical role in the cellular response to DNA damage.
  • EZH2 influences cancer cell sensitivity to DNA damage, suggesting therapeutic potential.
  • Targeting EZH2 may enhance the efficacy of conventional chemotherapy in malignancies.