Stem cells can become any type of cell in the body, but when NEIL1 and NEIL2 are missing, these cells lose the ability to become cranial neural crest cells. – who include some of the researchers involved in the 2016 study – have now used frog embryos and mouse embryonic stem cells to examine the role of the NEIL proteins in cranial neural crest cells. in 2016 showed that, in frogs, the absence of a similar protein called Neil2, leads to deformities of the face and skull.

On the other hand, they help remove a chemical group known as a methyl from DNA building blocks in a process called demethylation, which is involved both in development and disease. On the one hand, they help protect DNA from damage by acting as so-called ‘base excision repair enzymes’, meaning they remove damaged building blocks of DNA. NEIL1 and NEIL2 are mouse proteins with two roles. These types of abnormalities are among the most common birth defects known in humans. For example, the jaw- or cheekbones can be underdeveloped or there may be defects in the eyes or ears. When too few of these cells are made, the skull and the face can become deformed. The face of animals with a backbone is formed in great part by a group of cells called cranial neural crest cells. Thus, NEIL1 and NEIL2 DNA glycosylases protect mitochondrial DNA against oxidative damage during neural crest differentiation. Instead, Neil-deficiency results in oxidative damage specific to mitochondrial DNA, which triggers a TP53-mediated intrinsic apoptosis. Epistasis experiments with Tdg-deficient mESCs show no involvement of epigenetic DNA demethylation. Neil-deficiency elicits an oxidative stress-induced TP53-dependent DNA damage response, which impairs early cNCC specification. Neil-deficiency in Xenopus embryos and differentiating mouse embryonic stem cells (mESCs) leads to a surprisingly restricted defect in cranial neural crest cell (cNCC) development. Here we investigate the bifunctional DNA glycosylases/lyases NEIL1 and NEIL2, which act in repair of oxidative lesions and in epigenetic demethylation. This dual role raises the question if phenotypic abnormalities resulting from deficiency of BER factors are due to DNA damage or impaired DNA demethylation. Base excision repair (BER) functions not only in the maintenance of genomic integrity but also in active DNA demethylation and epigenetic gene regulation.

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