Alkyladenine DNA Glycosylases

Margulies, Carrie M; Samson, Leona D.

doi:10.1142/9789814719735_0005

Cited by 1 publication

(2 citation statements)

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“…An inefficient repair can lead to the accumulation of toxic lesions and, ultimately, apoptosis. For example, although base excision using a glycosylase is the first step in BER, higher amounts of these repair intermediates are more toxic than the parental damage if there are an insufficient amount of downstream repair proteins [ 37 ]. In addition, if a replication fork encounters a BER intermediate, the fork could collapse, resulting in a double-strand break [ 38 ], which can cause cell death if not repaired.…”

Section: Base Excision Repair (Ber) Mechanismsmentioning

confidence: 99%

“…AAG (or MPG ) KO showed some residual repair, but adding alkylating agents increased mutagenesis in splenic lymphocytes [ 82 , 83 ]. AAG is a unique glycosylase because it can identify various DNA substrates but cannot excise the lesion [ 37 ]. In some cell types, loss of function can increase its sensitivity to alkylating agents.…”

Section: Biology and Physiologymentioning

confidence: 99%

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

Gohil,

Sarker,

Roy

2023

IJMS

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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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Section: Base Excision Repair (Ber) Mechanismsmentioning

confidence: 99%