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Updated: Mar 19, 2026
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Laser Microirradiation to Study In Vivo Cellular Responses to Simple and Complex DNA Damage
Published on: January 31, 2018
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Phosphorylation and DNA damage resolution coordinate SOX2-mediated reprogramming in vivo.
Xiaoling Zhong1,2, Yuhua Zou1,2, Chun-Li Zhang1,2,3
1Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390.
Summary
Stem cell factor SOX2 reprograms glial cells into neurons. This process requires SOX2 phosphorylation and DNA repair via the nonhomologous end joining (NHEJ) pathway for central nervous system regeneration.
Area of Science:
- Neuroscience
- Stem cell biology
- Molecular mechanisms of reprogramming
Background:
- The transcription factor SOX2 can induce glial cells to become neurons in the adult mammalian brain.
- The precise molecular pathways governing this glial reprogramming are not fully understood.
Purpose of the Study:
- To elucidate the molecular mechanisms underlying SOX2-mediated in vivo glia-to-neuron reprogramming.
- To investigate the roles of SOX2 posttranslational modification and DNA repair pathways in this process.
Main Methods:
- Utilized SOX2 phosphorylation mutants and genetic manipulation of DNA repair pathways (PRKDC, KU80, LIG4).
- Assessed reprogramming efficiency in vivo in the adult mammalian central nervous system.
- Investigated the role of p53 in overcoming DNA damage-induced cell-cycle arrest during reprogramming.
Main Results:
- SOX2 phosphorylation and the PRKDC-dependent nonhomologous end joining (NHEJ) pathway are critical for SOX2-driven reprogramming.
- A phospho-mimetic SOX2 mutant enhanced reprogramming efficiency without changing neuronal fate.
- Disruption of PRKDC or core NHEJ components (KU80, LIG4) abolished reprogramming.
- p53 knockdown rescued reprogramming in PRKDC-deficient mice, suggesting a role in mitigating DNA damage responses.
Conclusions:
- SOX2-mediated glial reprogramming necessitates both specific posttranslational modifications of SOX2 and efficient DNA damage repair mechanisms.
- Targeting these pathways may offer novel strategies for enhancing central nervous system regenerative therapies.
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