Dumitrache, Lavinia C.;
Shimada, Mikio;
Downing, Susanna M.;
Kwak, Young Don;
Li, Yang;
Illuzzi, Jennifer L.;
Russell, Helen R.;
Wilson, David M.;
McKinnon, Peter J.
Apurinic endonuclease-1 preserves neural genome integrity to maintain homeostasis and thermoregulation and prevent brain tumors
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Media type:
E-Article
Title:
Apurinic endonuclease-1 preserves neural genome integrity to maintain homeostasis and thermoregulation and prevent brain tumors
Contributor:
Dumitrache, Lavinia C.;
Shimada, Mikio;
Downing, Susanna M.;
Kwak, Young Don;
Li, Yang;
Illuzzi, Jennifer L.;
Russell, Helen R.;
Wilson, David M.;
McKinnon, Peter J.
imprint:
Proceedings of the National Academy of Sciences, 2018
Published in:Proceedings of the National Academy of Sciences
Description:
<jats:title>Significance</jats:title>
<jats:p>The nervous system consumes a large quotient of oxygen and as such is at risk for high levels of oxidative DNA damage. A key DNA-repair factor, apurinic/apyrimidinic endonuclease 1 (APE1), is essential for repair of oxidative DNA lesions, although the specific role(s) for this enzyme in the nervous system is unknown. Surprisingly, mice lacking APE1 throughout neurogenesis were viable and showed little discernible phenotype at birth. However, after birth, when tissue oxygenation shifts from the placenta to respiration, loss of APE1 led to rapid and pronounced genome instability, resulting in widespread apoptosis, demyelination, thermoregulation defects, and brain tumors. Our findings reveal unrestrained oxidative DNA damage in the nervous system can result in specific pathology implicated in many human diseases.</jats:p>