Related Experiment Video

Updated: Jun 15, 2026

Visualization of DNA Repair Proteins Interaction by Immunofluorescence
07:55

Visualization of DNA Repair Proteins Interaction by Immunofluorescence

Published on: June 26, 2020

Interaction of the double-strand break repair kinase DNA-PK and estrogen receptor-alpha

Senad Medunjanin1, Sönke Weinert, Alexander Schmeisser

  • 1Internal Medicine, Department of Cardiology, Angiology, and Pneumology, Magdeburg University, 39120 Magdeburg, Germany. senad.medunjanin@med.ovgu.de

Molecular Biology of the Cell
|March 12, 2010
PubMed

Insights

DNA-dependent protein kinase (DNA-PK) phosphorylates estrogen receptor-alpha (ERalpha), stabilizing it and impacting breast cancer cell cycle progression. This highlights a novel role for DNA-PK in estrogen signaling pathways.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Signaling

Background:

  • Estrogens are implicated in proliferative diseases like breast cancer.
  • Estrogen receptor-alpha (ERalpha) activity is modulated by phosphorylation.
  • DNA-dependent protein kinase (DNA-PK) is crucial for DNA repair, cell cycle, and survival.

Purpose of the Study:

  • To investigate the hypothesis that DNA-PK modulates ERalpha signaling.
  • To explore the role of DNA-PK in ERalpha activity and breast cancer progression.

Main Methods:

  • Utilized a breast cancer cell line (MELN).
  • Investigated protein complex formation between DNA-PK and ERalpha upon estrogen stimulation.
  • Assessed ERalpha phosphorylation at Ser-118 using DNA-PK.
  • Examined ERalpha protein stability and degradation pathways.
  • Employed double-strand breaks and siRNA to modulate DNA-PK activity.

Main Results:

  • DNA-PK forms a complex with ERalpha in MELN cells after estrogen stimulation.
  • DNA-PK phosphorylates ERalpha at Ser-118, leading to protein stabilization.
  • Inhibition of DNA-PK results in proteasomal degradation of ERalpha.
  • Estrogen-induced ERalpha activation and cell cycle progression are partially dependent on DNA-PK activity.

Conclusions:

  • DNA-PK plays a significant role in regulating ERalpha stability and function.
  • DNA-PK-mediated phosphorylation of ERalpha is a key mechanism in estrogen signaling.
  • Targeting DNA-PK could represent a novel therapeutic strategy for ERalpha-positive breast cancers.

More Related Videos

Detecting the Ligand-binding Domain Dimerization Activity of Estrogen Receptor Alpha Using the Mammalian Two-Hybrid Assay09:07

Detecting the Ligand-binding Domain Dimerization Activity of Estrogen Receptor Alpha Using the Mammalian Two-Hybrid Assay

Published on: December 19, 2018

Assessment of Global DNA Double-Strand End Resection using BrdU-DNA Labeling coupled with Cell Cycle Discrimination Imaging06:44

Assessment of Global DNA Double-Strand End Resection using BrdU-DNA Labeling coupled with Cell Cycle Discrimination Imaging

Published on: April 28, 2021

Related Concept Videos

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...
Nucleotide Excision Repair01:08

Nucleotide Excision Repair

Overview
Nucleotide Excision Repair01:38

Nucleotide Excision Repair

DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
Long-patch Base Excision Repair01:02

Long-patch Base Excision Repair

Since the discovery of the two BER pathways, there has been a debate about how a cell chooses one pathway over the other and the factors determining this selection. Numerous in vitro experiments have pointed out multiple determinants for the sub-pathway selection. These are:
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...