A5062062407- HIV Research and Treatment
- CRISPR and Genetic Engineering
- Cytomegalovirus and herpesvirus research
- HIV/AIDS drug development and treatment
- HIV/AIDS Research and Interventions
- HIV-related health complications and treatments
- Ubiquitin and proteasome pathways
- Herpesvirus Infections and Treatments
- Biochemical and Molecular Research
- Epigenetics and DNA Methylation
- Diffusion and Search Dynamics
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- RNA Interference and Gene Delivery
- RNA modifications and cancer
- Prion Diseases and Protein Misfolding
- DNA and Nucleic Acid Chemistry
- Cancer-related gene regulation
- Virus-based gene therapy research
- Ethics in Clinical Research
- Cancer Genomics and Diagnostics
- Advanced biosensing and bioanalysis techniques
- DNA Repair Mechanisms
- Health Policy Implementation Science
- Virology and Viral Diseases
University of Saskatchewan
2012-2024
University of Alberta
2022-2024
Cytosine mutations within TCA/T motifs are common in cancer. A likely cause is the DNA cytosine deaminase APOBEC3B (A3B). However, A3B-null breast tumours still have this mutational bias. Here we show that APOBEC3H haplotype I (A3H-I) provides a solution to paradox. with bias at least one copy of A3H-I despite little genetic linkage between these genes. Although deemed inactive previously, has robust activity biochemical and cellular assays, similar A3H-II after compensation for lower...
The APOBEC3 deoxycytidine deaminase family functions as host restriction factors that can block replication of Vif (virus infectivity factor) deficient HIV-1 virions to differing degrees by deaminating cytosines uracils in single-stranded (−)HIV-1 DNA. Upon the (−)DNA (+)DNA, reverse transcriptase incorporates adenines opposite uracils, thereby inducing C/G→T/A mutations functionally inactivate HIV-1. Although both APOBEC3F and APOBEC3G are expressed cell types infects suppressed Vif, there...
The single-stranded DNA cytidine deaminases APOBEC3B, APOBEC3H haplotype I, and APOBEC3A can contribute to cancer through deamination of cytosine form promutagenic uracil in genomic DNA. enzymes must access during the dynamic processes replication or transcription, but enzymatic mechanisms enabling this activity are not known. To study this, we developed a method purify full length APOBEC3B characterized it comparison on substrates relevant mutagenesis. We found that ability an APOBEC3 cycle...
The human apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3 (APOBEC3, A3) family member proteins can deaminate cytosines in single-strand (ss) DNA, which restricts immunodeficiency virus type 1 (HIV-1), retrotransposons, and other viruses such as hepatitis virus, but cause a mutator phenotype many cancers. While structural information exists for several A3 proteins, the precise details regarding deamination target selection are not fully understood. Here, we report first...
Abstract APOBEC3G, a member of the double-domain cytidine deaminase (CD) APOBEC, binds RNA to package into virions and restrict HIV-1 through deamination-dependent or deamination-independent inhibition. Mainly due lack full-length APOBEC structure, it is unknown how CD1/CD2 domains connect dimerization/multimerization linked binding virion packaging for restriction. We report rhesus macaque A3G structures that show different inter-domain packing short linker refolding CD2. The dimer...
Human APOBEC3 enzymes are a family of single-stranded (ss)DNA and RNA cytidine deaminases that act as part the intrinsic immunity against viruses retroelements. These deaminate cytosine to form uracil which can functionally inactivate or cause degradation viral retroelement genomes. In addition, APOBEC3s have deamination independent antiviral activity through protein nucleic acid interactions. If expression levels misregulated, some access human genome leading mutagenesis, contributing...
APOBEC3H is a deoxycytidine deaminase that can restrict the replication of HIV-1 in absence viral protein Vif induces degradation cells. exists humans as seven haplotypes (I-VII) with different cellular stabilities. Of three stable (II, V, and VII), II V occur most frequently population. Despite being bona fide restriction factor, there has been no comparative biochemical characterization haplotypes. We characterized ssDNA scanning mechanisms use to search their substrate for...
The APOBEC3 (A3) enzymes, A3G and A3F, are coordinately expressed in CD4+ T cells can become coencapsidated into HIV-1 virions, primarily the absence of viral infectivity factor (Vif). A3F deoxycytidine deaminases that inhibit replication by inducing guanine-to-adenine hypermutation through deamination cytosine to form uracil minus-strand DNA. effect simultaneous presence both on restriction ability is not clear. Here, we used a single-cycle assay biochemical analyses determine if differ...
The Apolipoprotein B mRNA editing complex (APOBEC) family of enzymes contains single-stranded polynucleotide cytidine deaminases. These catalyze the deamination in RNA or DNA, which forms uracil. From this 11 member enzyme humans, DNA by seven APOBEC3 members is considered here. has many roles, such as restricting endogenous and exogenous retrovirus replication retrotransposon insertion events reducing DNA-induced inflammation. Similar to other APOBEC members, are a double-edged sword that...
The APOBEC3 enzymes can induce mutagenesis of HIV-1 proviral DNA through the deamination cytosine. overcomes this restriction viral protein Vif that induces proteasomal degradation. Within dynamic host-pathogen relationship, have been found to be beneficial, neutral, or detrimental biology. Here, we assessed ability co-expressed APOBEC3F and APOBEC3G resistance antiviral drugs. We co-expression enabled partial Vif-mediated degradation with a corresponding increase in APOBEC3F-induced...
Human APOBEC3 enzymes are a family of single-stranded (ss)DNA and RNA cytidine deaminases that act as part the intrinsic immunity against viruses retroelements. These deaminate cytosine to form uracil which can functionally inactivate or cause degradation viral retroelement genomes. In addition, APOBEC3s have deamination independent antiviral activity through protein nucleic acid interactions. If expression levels misregulated, some access human genome leading mutagenesis, contributing...
The APOBEC3 enzyme family are host restriction factors that induce mutagenesis of HIV-1 proviral genomes through the deamination cytosine to form uracil in nascent single-stranded (-)DNA. suppresses activity protein Vif induces degradation. Here we compared two common polymorphisms APOBEC3F. We found although both have activity, APOBEC3F 108 A/231V can restrict ΔVif up 4-fold more than S/231I and is partially protected from Vif-mediated This resulted higher levels steady state expression...