Complex Roles of NEIL1 and OGG1: Insights Gained from Murine Knockouts and Human Polymorphic Variants

DNA glycosylases promote genomic stability by initiating base excision repair (BER) in both the nuclear and mitochondrial genomes. Several of these enzymes have overlapping substrate recognition, through which a degree redundancy lesion recognition is achieved. For example, OGG1 NEIL1 recognize release imidazole-ring-fragmented guanine, FapyGua as part common overall pathway to cleanse genome damaged bases. However, many differences, including their differential breadth specificity, contrasting chemistries occurs, subsequent steps required complete BER pathway, identity specific protein-binding partners. Beyond complexities differences vivo biological roles been primarily elucidated studies murine models harboring knockout Neil1 or Ogg1, with diversity phenotypic manifestations exceeding what might anticipated for glycosylase deficiency. Pathologies associated deficiencies include cancer susceptibilities, where Ogg1-deficient mice are generally refractory carcinogenesis, while Neil1-deficient confer susceptibility. In contrast NEIL1, functions key transcription factor regulating inflammation other complex gene cascades. With regard phenotypes attributed repair, either genes results age- diet-induced metabolic syndrome. The adverse health consequences syndrome can be largely overcome expression mitochondrial-targeted human wild-type mice. goal this review compare that play maintaining integrity, emphasis on insights gained from not only diverse manifested transgenic mice, but also disease susceptibility polymorphic variants.