Base Excision Repair: Mechanisms and Impact in Biology, Disease, and Medicine.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, [2000-

Medicine*; Humans ; Animals ; Mice ; Mice, Knockout ; Aging ; DNA Repair ; Biology

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.

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R21 CA264489 United States CA NCI NIH HHS; P30 CA051008 United States CA NCI NIH HHS; P01 AG017242 United States AG NIA NIH HHS

Keywords: 5′-Gap; APE1; NEIL1/2; OGG1; PARP; PNKP; POL β; RECQ1; XPF-ERCC1; XRCC1; base excision repair (BER); nucleotide incision repair (NIR); replication-associated; transcription-associated

Date Created: 20230928 Date Completed: 20230929 Latest Revision: 20240926

20240926

PMC10531636

10.3390/ijms241814186

37762489