We reported a one-pot fluorescence-based assay to quantitively detect A3A activity combined with cytosine deamination and uracil excision. After deamination by A3A and USER enzyme treatment, the fluorescent turn-on effect at 520 nm was observed, which can be used to evaluate the A3A activity and screen inhibitors.
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http://dx.doi.org/10.1039/d1cb00076d | DOI Listing |
Proc Natl Acad Sci U S A
January 2025
Program in Genetics, Molecular, and Cellular Biology, Tufts University Graduate School of Biomedical Sciences, Boston, MA 02111.
CAG/CTG repeats are prone to expansion, causing several inherited human diseases. The initiating sources of DNA damage which lead to inaccurate repair of the repeat tract to cause expansions are not fully understood. Expansion-prone CAG/CTG repeats are actively transcribed and prone to forming stable R-loops with hairpin structures forming on the displaced single-stranded DNA (S-loops).
View Article and Find Full Text PDFAdv Sci (Weinh)
January 2025
Research Institute of Big Data Science and Industry, Shanxi University, Taiyuan, Shanxi, 030006, China.
The Streptococcus canis Cas9 protein (ScCas9) recognizes the NNG protospacer adjacent motif (PAM), offering a wider range of targets than that offered by the commonly used S. pyogenes Cas9 protein (SpCas9). However, both ScCas9 and its evolved Sc++ variant still exhibit low genome editing efficiency in plants, particularly at the less preferred NTG and NCG PAM targets.
View Article and Find Full Text PDFACS Chem Biol
January 2025
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 PDFHigh-grade serous ovarian cancer (HGSOC) is the most prevalent and aggressive histological subtype of ovarian cancer, and often presents with metastatic disease. The drivers of metastasis in HGSOC remain enigmatic. APOBEC3A (A3A), an enzyme that generates mutations across various cancers, has been proposed as a mediator of tumor heterogeneity and disease progression.
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