Cell birth, cell death, cell diversity and DNA breaks: how do they all fit together?
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Assessing Stem Cell DNA Integrity for Cardiac Cell Therapy
Published on: January 25, 2019
E C Gilmore1, R S Nowakowski, V S Caviness
1Department of Neuroscience, School of Medicine, Case Western Reserve University, University Hospitals of Cleveland, Cleveland, OH 44106, USA.
Abstract:
Substantial death of migrating and differentiating neurons occurs within the developing CNS of mice that are deficient in genes required for repair of double-stranded DNA breaks. These findings suggest that large-scale, yet previously unrecognized, double-stranded DNA breaks occur normally in early postmitotic and differentiating neurons. Moreover, they imply that cell death occurs if the breaks are not repaired. The cause and natural function of such breaks remains a mystery; however, their occurrence has significant implications. They might be detected by histological methods that are sensitive to DNA fragmentation and mistakenly interpreted to indicate cell death when no relationship exists. In a broader context, there is now renewed speculation that DNA recombination might be occurring during neuronal development, similar to DNA recombination in developing lymphocytes. If this is true, the target gene(s) of recombination and their significance remain to be determined.
Insights
Developing neurons undergo significant cell death if double-stranded DNA breaks are not repaired. This suggests normal DNA breaks occur during neuronal development, potentially impacting cell survival and research interpretation.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Developing neurons experience significant cell death in the central nervous system (CNS).
- Genes crucial for repairing double-stranded DNA breaks are essential for neuronal survival.
- Unrepaired double-stranded DNA breaks (DSBs) are implicated in neuronal cell death.
Purpose of the Study:
- To investigate the role of double-stranded DNA breaks (DSBs) in neuronal development and cell death.
- To explore the implications of DSBs on histological interpretations of neuronal cell death.
- To consider the possibility of DNA recombination during neuronal development.
Main Methods:
- Utilized mouse models deficient in genes responsible for double-stranded DNA break repair.
- Observed and analyzed neuronal cell death in the developing CNS.
- Interpreted findings in the context of DNA repair mechanisms and potential DNA recombination.
Main Results:
- Mice lacking functional DNA repair genes exhibit substantial death of migrating and differentiating neurons.
- Suggests that large-scale, previously unrecognized double-stranded DNA breaks occur normally in early postmitotic and differentiating neurons.
- Cell death ensues if these breaks are not adequately repaired.
Conclusions:
- Double-stranded DNA breaks (DSBs) are a normal occurrence during neuronal development and require repair for cell survival.
- The presence of DSBs may lead to misinterpretation of cell death in histological studies.
- The findings open avenues for investigating potential DNA recombination during neuronal development, analogous to lymphocyte development.
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