Affiliation:
1. Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057, USA
2. Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA
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.
Funder
National Institute of Health
Tobacco Related Diseases Research Program
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
Reference234 articles.
1. Mechanisms of DNA damage, repair, and mutagenesis;Chatterjee;Environ. Mol. Mutagen.,2017
2. Oxidative Stress: Harms and Benefits for Human Health;Pizzino;Oxid. Med. Cell. Longev.,2017
3. Background DNA damage for endogenous and unavoidable exogenous carcinogens: A basis for spontaneous cancer incidence?;Gupta;Mutat. Res.,1999
4. Carcinogens and DNA damage;Barnes;Biochem. Soc. Trans.,2018
5. DNA repair mechanisms in dividing and non-dividing cells;Iyama;DNA Repair.,2013
Cited by
5 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献