2020/07/10 by Gabrielle J. Grundy, Gabrielle J. Grundy, Jason L. Parsons +1 · 115 citations
Biochemistry, Genetics and Molecular Biology · Mathematics · Medicine · #Base (topology) #Base excision repair #Biology #Cancer #Cancer therapy #Cell death mechanisms and regulation #DNA Repair Mechanisms #DNA repair #Gene #Genetics #Internal medicine #Mathematics #Medicine #PARP inhibition in cancer therapy
paper · pdf · doi:10.1042/ebc20200013
published in Essays in Biochemistry 64(5), 831-843 (Portland Press)
openalex publication_date 2020/07/10 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/26
Base excision repair (BER) has evolved to preserve the integrity of DNA following cellular oxidative stress and in response to exogenous insults. The pathway is a coordinated, sequential process involving 30 proteins or more in which single strand breaks are generated as intermediates during the repair process. While deficiencies in BER activity can lead to high mutation rates and tumorigenesis, cancer cells often rely on increased BER activity to tolerate oxidative stress. Targeting BER has been an attractive strategy to overwhelm cancer cells with DNA damage, improve the efficacy of radiotherapy and/or chemotherapy, or form part of a lethal combination with a cancer specific mutation/loss of function. We provide an update on the progress of inhibitors to enzymes involved in BER, and some of the challenges faced with targeting the BER pathway.