Breaking bad: The mutagenic effect of DNA repair

Promulgator:SLSTRelease time:2015-05-15 Views:593

Species survival depends on the faithful replication of genetic information, which is continually monitored and maintained by DNA repair pathways that correct replication errors and the thousands of lesions that arise daily from the inherent chemical lability of DNA and the effects of genotoxic agents. The abnormality of DNA repair will cause numerous diseases including cancer. On the other hand, low frequency of mutagenesis could be a molecular force of evolution that can help species adapt to environmental changes. Neutrally evolving DNA (not under purifying selection,e.g., dead retrotransposon) accumulates base substitutions with time (the neutral mutation). Thus, studying the mechanism of neutral mutagenesis could reveal the molecular force of evolution. Recent studies found that the neutral mutation rate at non-CpG site is positively correlated with the local CpG content. As the C of CpG dinucleotides is methylated in mammals, spontaneous deamination of methyl-C generates a T/G mismatch. APOBEC/AID family of cytosine deaminase can induce mutations in flanking DNA during the repair of naturally occurring mismatches such as T/G, indicating that the mutagenesis of DNA repair could be a force that promotes evolution. However, cancer genomic studies recently showed that APOBEC/AID family of cytosine deaminase induced hypermutations in cancer patients (could account for up to 95% of total mutations), which suggests the connection of carcinogenesis and the DNA repair induced mutagenesis.


Dr. Jia Chen at School of Life Science and Technology, ShanghaiTech University and Dr. Anthony V. Furano at National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH) summarized the mechanism of DNA repair induced mutagenesis, its physiological and pathological impacts on organisms from the aspects of bioinformatics, biochemistry and molecular biology and highlighted the perspectives of DNA repair in cancer research on May 1st, 2015 online in DNA repair.


The review article with the title “Breaking bad: The mutagenic effect of DNA repair” published in DNA repair was supported by ShanghaiTech University start-up funds and the Intramural Research Program of NIH.


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