The human APOBEC3 gene cluster locus encodes polynucleotide cytidine deaminases. Although many act as viral restriction factors through mutation of single-stranded DNA, recent reports have shown that human APOBEC3A was capable of efficiently hypermutating nuclear DNA and inducing DNA breaks in genomic DNA. In addition, the enzyme was unique in efficiently deaminating 5-methylcytidine in single-stranded DNA. To appreciate the evolutionary relevance of these activities, we analyzed A3A-related enzymes from the rhesus and tamarin monkey, horse, sheep, dog, and panda. All proved to be orthologous to the human enzyme in all these activities revealing strong conservation more than 148 My. Hence, their singular role in DNA catabolism is a well-established mechanism probably outweighing any deleterious or pathological roles such as genomic instability and cancer formation.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1093/molbev/mst195 | DOI Listing |
J Biol Chem
December 2024
School of Environmental Science and Engineering, Shandong University, Qingdao 266237, China. Electronic address:
Base editing is preferable for bacterial gene inactivation without generating double strand breaks, requiring homology recombination or highly efficient DNA delivery capability. However, the potential of base editing is limited by the adjoined dependence on the editing window and protospacer adjacent motif (PAM). Herein, we report an unconstrained base editing system to enable the inactivation of any genes of interest (GOIs) in bacteria.
View Article and Find Full Text PDFMicrobiol Immunol
December 2024
Department of Microbiology, Faculty of Medicine, Shimane University, Izumo, Shimane, Japan.
Upon infection with the virus, cells increase the expression of cytidine deaminase APOBEC3 family genes. This leads to the accumulation of C-to-T mutations in the replicating viral genome and suppresses viral propagation. In contrast, herpesviruses, including Epstein-Barr virus (EBV), express genes that counteract APOBEC3 during lytic infection.
View Article and Find Full Text PDFACS Synth Biol
December 2024
The Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, China.
targeted mutagenesis technologies are the basis for the continuous directed evolution of specific proteins. Here, an efficient mutagenesis system (CgMutaT7) for continuous evolution of the targeted gene in was developed. First, cytosine deaminase and uracil-DNA glycosylase inhibitor were sequentially fused to T7 RNA polymerase using flexible linkers to build the CgMutaT7 system, which introduces mutations in targeted regions controlled by the T7 promoter.
View Article and Find Full Text PDFACS Chem Biol
December 2024
Department of Medicinal Chemistry, University of Minnesota, Minneapolis 55455, United States.
The APOBEC3 family of polynucleotide cytidine deaminases has diverse roles as viral restriction factors and oncogenic mutators. These enzymes convert cytidine to uridine in single-stranded (ss)DNA, inducing genomic mutations that promote drug resistance and tumor heterogeneity. Of the seven human APOBEC3 members, APOBEC3A (A3A) and APOBEC3B (A3B) are most implicated in driving pro-tumorigenic mutations.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!