Targeting base excision repair suggests a new therapeutic strategy of fludarabine for the treatment of chronic lymphocytic leukemia

The C-terminal Domain (CTD) of Human DNA Glycosylase NEIL1 Is Required for Forming BERosome Repair Complex with DNA Replication Proteins at the Replicating Genome

“…A variety of oxidized base lesions in mammalian genomes, induced by endogenous reactive oxygen species, both spontaneously generated during cellular metabolism and generated by several genotoxic agents, including ionizing radiation, are repaired via the base excision repair (BER) 4 pathway (1). Many among the mutagenic and cytotoxic oxidized bases contribute to cellular sensitivity to ionizing radiation as well as radiomimetic and other drugs used in cancer therapy.…”

“…Their repair, which contributes to drug resistance, depends on BER competency of the cells. Thus, various strategies to target the BER pathway are being explored for sensitizing cancer cells as an adjuvant therapy modality with radiation or radiomimetic drugs (2)(3)(4).…”

Targeting DNA repair with aphidicolin sensitizes primary chronic lymphocytic leukemia cells to purine analogs

“…Nevertheless, sensitization of CLL cells to fludarabine has been reported in the presence of NU7441, which impairs the NHEJ pathway through inhibition of DNA-dependent protein kinase [35], and methoxyamine, a BER inhibitor [36]. In addition, cladribine cytotoxicity was increased in NER-deficient lymphoblasts compared to wild-type cells [37].…”

“…Although the sample size was limited and p53 dysfunction might not be complete, these data suggest that increase of cell death induced by aphidicolin could occur by p53-dependent and -independent mechanisms. That DNA damage can induce signaling for apoptosis in a p53-independent manner has recently became increasingly evident from literature data in different types of cancer cells including the leukemic cell line HL-60 and primary CLL cells [35, 36, 43]. …”

Association of a Newly Identified Variant of DNA Polymerase Beta (polβΔ63-123, 208-304) with the Risk Factor of Ovarian Carcinoma in India

“…One of the reasons for the chemo-resistance is due to overexpression of the proteins of base excision repair (BER) pathway, particularly DNA polymerase beta (polβ). Hence, it is logical to sensitize the cancer cells by suppressing the polβ protein and then treat the patients with chemo; thereby the therapy would be effective (Liu et al, 2004;Bulgar et al, 2010). If the polβ protein is being mutated then the function will be altered.…”