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Author Spotlight: Understanding DNA Damage Response in Mammalian Oocytes and Preimplantation Embryos
Published on: June 23, 2023
Central and Peripheral Expression of DNA Double-Strand Breaks in Human and Mouse Tissues
Mia P Castiglione1, Raddy L Ramos1, Joerg R Leheste1
1Department of Biomedical Sciences, New York Institute of Technology, College of Osteopathic Medicine, Old Westbury, New York, 11568.
Abstract:
Mammalian cells accumulate DNA lesions when they undergo phases of the cell cycle or during normal cellular activity. In this regard, several DNA repair signaling pathways have evolved to maintain genome stability and avoid the potential acquisition of mutations. To define and further characterize the expression of DNA double-strand breaks in humans and mice, we used immunocytochemistry to localize a DNA damage signal within the spatial confines of the cell nucleus. We show that DNA double-strand breaks are abundantly expressed in postmitotic neurons of the human and mouse brain. Notably, DNA double-strand breaks are present in human hypothalamic and mouse striatal and hippocampal cells, with stable expression of the nuclear signal detected throughout the mammalian brain. Analysis of the mouse tongue, heart, and testis shows that expression of DNA double-strand breaks is only demonstrated in circumscribed populations of peripheral cells. These data suggest that levels of DNA double-strand breaks are tissue-specific with the tongue, heart and testicular tissue having different thresholds of DNA repair and DNA damage from those outlined at the brain level. Anat Rec, 301:1251-1257, 2018. © 2018 Wiley Periodicals, Inc.
Insights
DNA double-strand breaks are abundant in mammalian brain neurons but scarce in peripheral tissues, indicating tissue-specific DNA damage and repair thresholds. This finding highlights differences in genome maintenance across cell types.
Area of Science:
- Cell Biology
- Genetics
- Neuroscience
Background:
- Mammalian cells face DNA lesions during cell cycle and normal activity.
- DNA repair pathways are crucial for genome stability and mutation prevention.
Purpose of the Study:
- To characterize the expression and localization of DNA double-strand breaks (DSBs) in human and mouse cells.
- To investigate tissue-specific differences in DSB accumulation and DNA repair.
Main Methods:
- Immunocytochemistry was employed to detect and localize DSBs within the cell nucleus.
- Analysis was performed on brain tissues (human hypothalamus, mouse striatum and hippocampus) and peripheral tissues (mouse tongue, heart, testis).
Main Results:
- DSBs were abundantly expressed in postmitotic neurons throughout the mammalian brain.
- DSBs were found in specific populations of peripheral cells in the tongue, heart, and testis.
- Expression levels of DSBs varied significantly between brain and peripheral tissues.
Conclusions:
- DSB accumulation is tissue-specific, suggesting differential DNA repair capacities.
- The brain exhibits a higher baseline level of DSBs compared to the analyzed peripheral tissues.
- These findings contribute to understanding genome maintenance and DNA damage thresholds in different mammalian cell types.
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