NEIL1 and NEIL2 DNA glycosylases protect neural crest development against mitochondrial oxidative stress

• DOI: 10.7554/elife.49044
• Publication Date: 2019-09-30T11:19:03Z
• Authors: Dandan Han; Lars Schomacher; Katrin M Schüle; Medhavi Mallick; Michael U Musheev; Emil Karaulanov; Laura Krebs; Annika von Seggern; Christof Niehrs
• Keywords: DNA demethylation

Base excision repair (BER) functions not only in the maintenance of genomic integrity but also active DNA demethylation and epigenetic gene regulation. This dual role raises question if phenotypic abnormalities resulting from deficiency BER factors are due to damage or impaired demethylation. Here we investigate bifunctional glycosylases/lyases NEIL1 NEIL2, which act oxidative lesions Neil-deficiency Xenopus embryos differentiating mouse embryonic stem cells (mESCs) leads a surprisingly restricted defect cranial neural crest cell (cNCC) development. elicits an stress-induced TP53-dependent response, impairs early cNCC specification. Epistasis experiments with Tdg-deficient mESCs show no involvement Instead, results specific mitochondrial DNA, triggers TP53-mediated intrinsic apoptosis. Thus, NEIL2 glycosylases protect against during differentiation.