1. Base Excision Repair: Mechanisms and Impact in Biology, Disease, and Medicine
- Author
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Gohil, Dhara, Sarker, Altaf H, and Roy, Rabindra
- Subjects
Biochemistry and Cell Biology ,Biological Sciences ,Genetics ,Aging ,2.1 Biological and endogenous factors ,Aetiology ,Humans ,Animals ,Mice ,Mice ,Knockout ,Medicine ,DNA Repair ,Biology ,5′-Gap ,APE1 ,NEIL1/2 ,OGG1 ,PARP ,PNKP ,POL β ,RECQ1 ,XPF-ERCC1 ,XRCC1 ,base excision repair ,nucleotide incision repair ,replication-associated ,transcription-associated ,Other Chemical Sciences ,Other Biological Sciences ,Chemical Physics ,Biochemistry and cell biology ,Microbiology ,Medicinal and biomolecular chemistry - Abstract
Base excision repair (BER) corrects forms of oxidative, deamination, alkylation, and abasic single-base damage that appear to have minimal effects on the helix. Since its discovery in 1974, the field has grown in several facets: mechanisms, biology and physiology, understanding deficiencies and human disease, and using BER genes as potential inhibitory targets to develop therapeutics. Within its segregation of short nucleotide (SN-) and long patch (LP-), there are currently six known global mechanisms, with emerging work in transcription- and replication-associated BER. Knockouts (KOs) of BER genes in mouse models showed that single glycosylase knockout had minimal phenotypic impact, but the effects were clearly seen in double knockouts. However, KOs of downstream enzymes showed critical impact on the health and survival of mice. BER gene deficiency contributes to cancer, inflammation, aging, and neurodegenerative disorders. Medicinal targets are being developed for single or combinatorial therapies, but only PARP and APE1 have yet to reach the clinical stage.
- Published
- 2023