The Tardigrade damage suppressor protein Dsup promotes DNA damage in neurons.
Mol Cell Neurosci
; 125: 103826, 2023 06.
Article
em En
| MEDLINE
| ID: mdl-36858083
ABSTRACT
Tardigrades are microscopic invertebrates, which are capable of withstanding extreme environmental conditions, including high levels of radiation. A Tardigrade protein, Dsup (Damage Suppressor), protects the Tardigrade's DNA during harsh environmental stress and X-rays. When expressed in cancer cells, Dsup protects DNA from single- and double-strand breaks (DSBs) induced by radiation, increases survival of irradiated cells, and protects DNA from reactive oxygen species. These unusual properties of Dsup suggested that understanding how the protein functions may help in the design of small molecules that could protect humans during radiotherapy or space travel. Here, we investigated if Dsup is protective in cortical neurons cultured from rat embryos. We discovered that, in cortical neurons, the codon-optimized Dsup localizes to the nucleus and, surprisingly, promotes neurotoxicity, leading to neurodegeneration. Unexpectedly, we found that Dsup expression results in the formation of DNA DSBs in cultured neurons. With electron microscopy, we discovered that Dsup promotes chromatin condensation. Unlike Dsup's protective properties in cancerous cells, in neurons, Dsup promotes neurotoxicity, induces DNA damage, and rearranges chromatin. Neurons are sensitive to Dsup, and Dsup is a doubtful surrogate for DNA protection in neuronal cells.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Dano ao DNA
/
Cromatina
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Mol Cell Neurosci
Assunto da revista:
BIOLOGIA MOLECULAR
/
NEUROLOGIA
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos