Base excision repair: A critical player in many games

Abstract

This perspective reviews the many dimensions of base excision repair from a 10,000 foot vantage point and provides one person’s view on where the field is headed. Enzyme function is considered under the lens of X-ray diffraction and single molecule studies. Base excision repair in chromatin and telomeres, regulation of expression and the role of posttranslational modifications are also discussed in the context of enzyme activities, cellular localization and interacting partners. The specialized roles that base excision repair play in transcriptional activation by active demethylation and targeted oxidation as well as how base excision repair functions in the immune processes of somatic hypermutation and class switch recombination and its possible involvement in retroviral infection are also discussed. Finally the complexities of oxidative damage and its repair and its link to neurodegenerative disorders, as well as the role of base excision repair as a tumor suppressor are examined in the context of damage, repair and aging. By outlining the many base excision repair-related mysteries that have yet to be unraveled, hopefully this perspective will stimulate further interest in the field.

Genetic Single Nucleotide Polymorphisms (GSNPs) in the DNA Repair Genes and Hepatocellular Carcinoma Related to Aflatoxin B1 among Guangxiese Population

“…As described previously [60], DNA glycosylases play a central role in the BER pathway because they can recognize and catalyze the removal of damaged bases. Among having been reported GSNPs in DNA glycosylase-encoded genes, only hOGG1 correlates with DNA repair capacity [5,61].…”

Unveiling the non-repair face of the Base Excision Repair pathway in RNA processing: A missing link between DNA repair and gene expression?

“…the 8-oxoguanine DNA glycosylase − OGG1) deputed to cleave the DNA backbone leaving a 3′-α,β-unsaturated aldehyde blocking group. An additional family of DNA glycosylases, represented by the human NEIL1 and NEIL2 enzymes, is also able to operate a β,δ-elimination reaction, leaving a 3′-phosphate nick [2]. Higher eukaryotes are provided with a vast array of DNA glycosylases with a significant redundancy in their damage selectivity for this reason, single knockout of several DNA glycosylases is not lethal per se, although an accumulation of unrepaired DNA lesions occurs [3].…”

Base Excision Repair Manipulation in Breast Carcinoma: A Prospective Avenue to Potentiate Genome Insulting Approach

“…The BER protects the genome of the organism from various DNA damages caused by oxidation, alkylation and deamination [39]. BER system is a highly conserved system employed from bacteria to humans responsible for the removal of a large number of endogenous DNA damages which include deamination, depurination and alkylation [39].…”