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Updated: Jun 8, 2026
13:10
Detection and Visualization of DNA Damage-induced Protein Complexes in Suspension Cell Cultures Using the Proximity Ligation Assay
Published on: June 9, 2017
Dynamic changes to survivin subcellular localization are initiated by DNA damage
Maritess Gay Asumen1, Tochukwu V Ifeacho, Luke Cockerham
1Touro University's College of Osteopathic Medicine, Vallejo, CA, USA;
Oncotargets and Therapy
|September 22, 2010
Summary
The apoptosis inhibitor survivin
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Survivin is an apoptosis inhibitor with a hypothesized link between its subcellular localization and function.
- DNA damage-sensing protein kinases, including ATM, ATR, and DNA-PK, are crucial for propagating DNA damage signals.
- The subcellular distribution of survivin can change based on cell cycle phase or therapeutic insults.
Purpose of the Study:
- To investigate the role of DNA damage-sensing protein kinases in the UV-induced subcellular repartitioning of survivin.
- To determine if specific kinases are responsible for survivin's mitochondrial redistribution upon DNA damage.
- To explore the functional implications of survivin's dynamic subcellular distribution in response to DNA damage.
Main Methods:
- Utilizing MCF-7 cells treated with UV light to induce DNA damage.
- Employing the pan PIK kinase inhibitor wortmannin to assess the involvement of PIK kinases.
- Analyzing survivin localization in cells with deficiencies in DNA damage-sensing protein kinases (ATM, ATR, DNA-PK).
Main Results:
- UV light-induced subcellular repartitioning of survivin in MCF-7 cells is dependent on DNA damage-sensing proteins.
- Wortmannin treatment caused survivin to redistribute to mitochondria and decrease in the cytosol and nucleus.
- Mitochondrial redistribution of survivin occurred in cells lacking DNA-PK, ATM, or ATR.
- Survivin redistribution failure upon low-dose UV exposure was observed exclusively in ATM-deficient cells, implicating ATM as a primary kinase in this process.
Conclusions:
- Survivin's subcellular distribution is a dynamic process responsive to UV light-induced DNA damage.
- ATM appears to be the primary kinase involved in survivin's redistribution from mitochondria in response to UV damage.
- The dynamic subcellular localization of survivin may underlie its multifunctionality.
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