Program DHC-Virtual
20 - 21 January 2021
Abstracts Myeloid session 2
Abstract
Is there a role for nuclear DNA sensors in anthracycline induced cell death?
20 January
10:24 10:36
S. van der Zanden
Paper

Is there a role for nuclear DNA sensors in anthracycline induced cell death?

Sabina van der Zanden (1), Leonie Hamoen (1), Merle van Gelder (1), Jacques Neefjes (1)
(1) LUMC, Cell and Chemical Biology, Leiden
No potential conflicts of interest
Introduction

 

The anthracycline drugs doxorubicin and its analogues epirubicin and daunorubicin are cornerstones in the treatment of different types of hematological and solid tumors for over half a century. However, the exact molecular mechanism by which these drugs function is still not fully understood. A well accepted mechanism of action is the formation of DNA damage, via interference with the catalytic cycle of topoisomerase II. A recently discovered second mechanism – chromatin damage as the result of histone eviction – was shown to be the main cytotoxic mechanism of these drugs. How histone eviction subsequently leads to the induction of cell death is poorly understood. 

Methods

Using various molecular biological techniciques we identify three nuclear DNA sensors that might be involved in chromatin damage mediated cell death.

Results

We show that the nuclear DNA sensors (IFI16, IFIX and MNDA), active in the innate immune response to DNA viruses, specifically re-localize to DNA upon histone eviction, and identify novel interaction partners for these sensors. 

 

Conclusion

Nuclear DNA sensors might play a role in anthracycline-induced cytotoxicity.

 

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