2017 (Click to expand/collapse year)
Richards C.M., Li M., Perkins A.L., Rathore A., Harki D.A., & Harris RS. (2017) Reassessing APOBEC3G Inhibition by HIV-1 Vif-Derived Peptides. Journal of Molecular Biology, 429(1):88-96. Jan 7.
›Brief description: The Vif-derived peptide, Vif 25-39, does not inhibit APOBEC3G enzymatic activity and Vif 105-119 acts non-specifically on A3G.Starrett G.J., Marcelus C., Cantalupo P.G., Katz J.P., Cheng J., Akagi K., Thakuria M., Rabinowits G., Wang L.C., Symer D.E., Pipas J.M., Harris R.S., & DeCaprio JA. (2017) Merkel Cell Polyomavirus Exhibits Dominant Control of the Tumor Genome and Transcriptome in Virus-Associated Merkel Cell Carcinoma. mBio 8(1), pii: e02079-16. Jan 3.
›Brief description: Whole transcriptome and genome analyses of Merkel cell carcinomas reveal distinct mutation patterns between virus+ and virus- tumors.
2016 (Click to expand/collapse year)
Shi K., Carpenter M.A., Banerjee S., Shaban N.M., Kurahashi K., Salamango D.J., McCann J.L., Starrett G.J., Duffy J.V., Demir Ö., Amaro R.E., Harki D.A., Harris R.S., & Aihara H. (2016) Structural basis for targeted DNA cytosine deamination and mutagenesis by APOBEC3A and APOBEC3B. Nature Structure & Molecular Biology, epub ahead of print. Dec 19.
›Brief description: First crystal structures of APOBEC3A and APOBEC3B bound to ssDNA reveal models for DNA binding and substrate preference.Harris R.S. & Anderson B.D. (2016) Evolutionary Paradigms from Ancient and Ongoing Conflicts between the Lentiviral Vif Protein and Mammalian APOBEC3 Enzymes. PLoS Pathogens, 12(12):e1005958. Dec 1.
›Brief description: Educational Pearl on lentiviral Vif proteins and APOBEC3 diversity with a proposed evolutionary "Wobble Model" for host-pathogen interaction dynamics.Law E.K., Sieuwerts A.M., LaPara K., Leonard B., Starrett G.J., Molan A.M., Temiz N.A., Vogel R.I., Meijer-van Gelder M.E., Sweep F.C., Span P.N., Foekens J.A., Martens J.W., Yee D., & Harris R.S. (2016) The DNA cytosine deaminase APOBEC3B promotes tamoxifen resistance in ER-positive breast cancer. Science Advances, 2(10):e1601737. Oct 7.
›Brief description: APOBEC3B expression is inversely correlated with survival in mice with ER+ breast tumors treated with tamoxifen and accelerates drug resistance.Starrett G.J., Luengas E.M., McCann J.L., Ebrahimi D., Temiz N.A., Love R.P., Feng Y., Adolph M.B., Chelico L., Law E.K., Carpenter M.A., & Harris R.S. (2016) The DNA cytosine deaminase APOBEC3H haplotype I likely contributes to breast and lung cancer mutagenesis. Nature Communications, 7:12918. Sep 21.
›Brief description: Identification of APOBEC3H-I as a source of mutation in cancer.Akre M.K., Starrett G.J., Quist J.S., Temiz N.A., Carpenter M.A., Tutt A.N., Grigoriadis A., & Harris R.S. (2016) Mutation Processes in 293-Based Clones Overexpressing the DNA Cytosine Deaminase APOBEC3B. PLoS One, 11(5):e0155391. May 10.
›Brief description: Conditional and isogenic system for APOBEC3B idunction, genomic DNA deamination, and mutagenesis reveals global increases in C-to-T mutations.Verhalen B., Starrett G.J., Harris R.S., & Jiang M. (2016) Functional Upregulation of the DNA Cytosine Deaminase APOBEC3B by Polyomaviruses. Journal of Virology, 90(14):6379-86. May 16.
›Brief description: APOBEC3B is upregulated by BK polyomavirus(PyV) infection in primary kidney cells and may contribute to PyV-mediated tumorigenesis.Shaban N.M., Shi K., Li M., Aihara H., & Harris R.S. (2016) 1.92 Angstrom Zinc-Free APOBEC3F Catalytic Domain Crystal Structure. Journal of Molecular Biology, 428(11):2307-16. Jun 5.
›Brief description: First zinc-free cystal structure of APOBEC3F reveals conserved active site residues involved in zinc coordination.Leonard B., Starrett G.J., Maurer M.J., Oberg A.L., Van Bockstal M., Van Dorpe J., De Wever O., Helleman J., Sieuwerts A.M., Berns E.M., Martens J.W., Anderson B.D., Brown W.L., Kalli K.R., Kaufmann S.H.,& Harris R.S. (2016) APOBEC3G Expression Correlates with T-Cell Infiltration and Improved Clinical Outcomes in High-grade Serous Ovarian Carcinoma. Clinical Cancer Research, 22(18):4746-55. Epub March 25.
›Brief description: APOBEC3G expression correlates with several T cell genes in HGSOC and is a novel candidate biomarker for infiltrating T lymphocytes.
›Brief description: Elucidation of APOBEC3F-Vif interface lends insight to the evolution of essential virus-host interactions, explained through a wobble model.Anderson, B.D. & Harris R.S. (2015) Transcriptional regulation of APOBEC3 antiviral immunity through the CBF-β/RUNX axis. Science Advances, 1(8):e1500296.
›Brief description: Disruption of normal CBFβ functions by HIV-1 Vif regulates APOBEC3 levels at both the transcriptional and post-translational levels.Land A.M., Wang J., Law E.K., Aberle R., Kirmaier A., Krupp A., Johnson W.E., & Harris R.S. (2015) Degradation of the cancer genomic DNA deaminase APOBEC3B by SIV Vif. Oncotarget, 6(37):39969-79.
›Brief description: SIV Vif promotes the degradation of endogenous APOBEC3B in cancer cell lines and prevent APOBEC3B-mediated geno/cytotoxicity.Leonard B., McCann J.L., Starrett G.J., Kosyakovsky L., Luengas E.M., Molan A.M., Burns M.B., McDougle R.M., Parker P.J., Brown W.L., & Harris R.S. (2015) The PKC/NF-κB signaling pathway induces APOBEC3B expression in multiple human cancers. Cancer Research, 5(21):4538-47.
›Brief description: PKC activation leads to upregulation of APOBEC3B in cancer cell lines by recruiting RELB to the APOBEC3B promoter.Shi K., Carpenter M.A., Kurahashi K., Harris R.S., & Aihara H. (2015) Crystal Structure of the DNA deaminase APOBEC3B catalytic domain. Journal of Biological Chemistry, 290(47):28120-30.
›Brief description: First high-resolution crystal structures of APOBEC3B catalytic domain highlights the residues required for APOBEC3B catalysis.Olson M.E., Abate-Pella D., Perkins A.L., Li M., Carpenter M.A., Rathore A., Harris R.S., & Harki D.A. (2015) Oxidative Reactivities of 2-Furylquinolines: Ubiquitous Scaffolds in Common High-Throughput Screening Libraries. Journal of Medicinal Chemistry, 58(18), 7419-30.
›Brief description: Identification of a potent small molecule inhibitor of APOBEC3G by high throughput screening and decomposition analysis.Swanton C., McGranahan N., Starrett G.J., & Harris R.S. (2015) APOBEC Enzymes: Mutagenic Fuel for Cancer Evolution and Heterogeneity. Cancer Discovery, 5(7), 704-12.
›Brief description: This review examines the role of deregulated APOBEC3 enzyme activity in promoting tumor subclonal expansion and intratumor heterogeneity.Kouno T., Luengas E.M., Shigematsu M., Shandilya S.M., Zhang J., Chen L., Hara M., Schiffer C.A., Harris R.S., & Matsuo H. (2015) Structure of the Vif-binding domain of the antiviral enzyme APOBEC3G. Nature Structural and Molecular Biology, 22(6), 485-91.
›Brief description: First structure of the APOBEC3G N-terminal domain reveals the Vif- interacting surface formed by the α1-β1, β2-α2 and β4-α4 loops.Kane J.R., Stanley D.J., Hultquist J.F., Johnson J.R., Mietrach N., Binning J.M., Jónsson S.R., Barelier S., Newton B.W., Johnson T.L., Franks-Skiba K.E., Li M., Brown W.L., Gunnarsson H.I., Adalbjornsdóttir A., Fraser J.S., Harris R.S., Andrésdóttir V., Gross J.D., & Krogan N.J. (2015) Lineage-Specific Viral Hijacking of Non-canonical E3 Ubiquitin Ligase Cofactors in the Evolution of Vif Anti-APOBEC3 Activity. Cell Reports, 11(8), 1236-50.
›Brief description: Comparison of Vif cofactors among HIV-1, SIV, FIV, BIV, and MVV lentiviruses reveals that CBF is dispensable for non-primate Vif proteins, no cofactor is required for BIV Vif, and cyclophilin A is a novel cofactor for MVV Vif.Harris, R.S. (2015) Molecular mechanism and clinical impact of APOBEC3B-catalyzed mutagenesis in breast cancer. Breast Cancer Research, 17, 8.
›Brief description: This review describes the role of APOBEC3B as a source of DNA damage in cancers and its clinical impact on breast cancer prognosis.Harris, R.S., & Dudley, J.P. (2015) APOBECs and virus restriction. Virology, 479-480, 131-45.
›Brief description: This review highlights various mechanisms of APOBEC3 enzyme inhibition by viral pathogens such as HIV, HTLV-1, MMTV, MuLV, endogenous retroviruses, and DNA viruses.
›Brief description: The alpha3 and alpha4 helices of human APOBEC3F are important determinants of the interaction with HIV-1 Vif.Albin J.S., Brown W.L., & Harris R.S. (2014) Catalytic activity of APOBEC3F in required for efficient restriction of Vif-deficient human immunodeficiency virus. Virology.
›Brief description: Catalytically active A3F is required for efficient restriction of Vif-deficient and susceptible HIV Vif mutants.Vieira V.C., Leonard B., White E.A., Starrett G.J., Temiz N.A., Lorenz L.D., Lee D., Soares M.A., Lambert P.F., Howley P.M., & Harris R.S. (2014) Human papillomavirus E6 triggers upregulation of the antiviral and cancer genomic DNA deaminase APOBEC3B. mBio, 5(6).
›Brief description: APOBEC3B is upregulated in HPV-positive cancers and endogenous high-risk HPV E6 oncoprotein is required for APOBEC3B upregulation.Refsland E.W., Hultquist J.F., Luengas E.M., Ikeda T., Shaban N.M., Law E.K., Brown W.L., Reilly C., Emerman M., & Harris R.S. (2014) Natural polymorphisms in human APOBEC3H and HIV-1 Vif combine in primary T lymphocytes to affect viral G-to-A mutation levels and infectivity. PLOS Genetics.
›Brief description: Dynamic interactions between host APOBEC3H polymorphisms and HIV-1 Vif variations contribute to differential resistance to infection in CD4+ T cells.
›Brief description: A3Bis active in the nucleus of several ovarian cancer cell lines and A3B expression correlates with total mutational load in in early-stage, high-grade ovarian cancers.Rathore, A., M.A. Carpenter, Ö. Demir, T. Ikeda, M. Li, N.M. Shaban, E.K. Law, D. Anokhin, W.L. Brown, R.E. Amaro, & R.S. Harris. (2013) The Local Dinucleotide Preference of APOBEC3G Can Be Altered from 5'-CC to 5'-TC by a Single Amino Acid Substitution. Journal of Molecuar Biology, Epub: Aug 11.
›Brief description: This paper determines the amino acid determinants that govern 5′-CC and 5′-TC demaination context preferences.
Burns M.B., N.A. Temiz, & R.S. Harris. (2013) Evidence for APOBEC3B mutagenesis in multiple human cancers. Nature Genetics, 45, 977-83.
›Brief description: This publication examines the expression profiles and exomic sequences of 19 different human cancers, and identifies 6 cancer types that are likely to be affected by APOBEC3B.
Refsland E.W. & R.S. Harris. (2013) The APOBEC3 family of retroelement restriction factors. Current Topics in Microbiology and Immunology, 371, 1-27.
›Brief description: This comprehensive review details the role of the APOBEC3 family of cytosine deaminases in both innate immunity and cancer.
Bohn M., S.M. Shandilya, J.S. Albin, T. Kouno, B.D. Anderson, R.M. McDougle, M.A. Carpenter, A. Rathore, L. Evans, A.N. Davis, J. Zhang, Y. Lu, M. Somasundaran, H. Matsuo, R.S. Harris, & C.A. Schiffer. (2013) Crystal structure of the DNA cytosine deaminase APOBEC3F: the catalytically active and HIV-1 Vif-binding domain. Structure, 21, 1042-50.
›Brief description: This study reports the crystal structure of the HIV Vif binding, catalytically active, C-terminal domain of APOBEC3F (A3F-CTD).
Land A.M., E.K. Law, M.A. Carpenter, L. Lackey, W.L. Brown, & R.S. Harris. (2013) Endogenous APOBEC3A DNA cytosine deaminase is cytoplasmic and nongenotoxic. Journal of Biological Chemistry, 288, 17253-60.
›Brief description: This paper reveals that, in contrast to transgenic APOBEC3A, endogenous APOBEC3A localizes to the cytoplasm of cells and is therefore unlikely to access and deaminate genomic DNA.
Burns M.B., L. Lackey, M.A. Carpenter, A. Rathore, A.M. Land, B. Leonard, E.W. Refsland, D. Kotandeniya, N. Tretyakova, J.B. Nikas, D. Yee, N.A. Temiz, D.E. Donohue, R.M. McDougle, W.L. Brown, E.K. Law, & R.S. Harris. (2013) APOBEC3B is an enzymatic source of mutation in breast cancer. Nature, 494, 366-70.
›Brief description: This paradigm shifting publication identifies APOBEC3B as a novel, endogenous source of mutation in breast cancer.
›Brief description: This paper describes the synthesis and biochemical evaluation of a class of 4-amino-1,2,4-triazole-3-thiol small-molecules as inhibitors of APOBEC3G.
Harris R.S., J.F. Hultquist, & D.T. Evans. (2012) The restriction factors of human immunodeficiency virus. Journal of Biological Chemistry, 287, 40875-83.
›Brief description: This review outlines the general hallmarks of restriction factors and provides an in-depth description of three classes of protiens that are known to restrict HIV.
Carpenter M.A., M. Li, A. Rathore, L. Lackey, E.K. Law, A.M. Land, B.Leonard, S.M. Shandilya, M. Bohn, C.A. Schiffer, W.L. Brown, & R.S. Harris. (2012) Methylcytosine and normal cytosine deamination by the foreign DNA restriction enzyme APOBEC3A. Journal of Biological Chemistry, 287, 34801-8.
›Brief description: This paper shows that APOBEC3A has the ability to deaminate methylated cytosines both in vitro and in vivo, suggesting a potential role in epigenome maintenance.
Refsland, E.W., J.F. Hultquist, & R.S. Harris. (2012) Endogenous Origins of HIV-1 G-to-A Hypermutation and Restriction in the Nonpermissive T Cell Line CEM2n. PLoS Pathogens, 8, e1002800.
›Brief description: This paper uses rAAV mediated gene targeting to generate APOBEC3F and APOBEC3G knockout T cell lines and demonstrates that APOBEC3D, APOBEC3F, and APOBEC3G contriubute to HIV-1 restriction and hypermutation.
Hultquist, J.F., R.M. McDougle, B.D. Anderson, & R.S. Harris. (2012) HIV-1 Vif and the RUNX Transcription Factors Interact with CBFβ on Genetically Distinct Surfaces. AIDS Research and Human Retroviruses, Epub: Jun 22.
›Brief description: This paper identifies a single amino acid change in CBFβ that disrupts its functional and physical interaction with HIV-1 Vif while maintaining its interaction with RUNX1.
Lackey, L., Z.L. Demorest, A.M. Land, J.F. Hultquist, W.L. Brown, & R.S. Harris. (2012) APOBEC3B and AID have similar nuclear import mechanisms. Journal of Molecular Biology, 419, 301-314.
›Brief description: This paper finds mechanistic conservation between the nuclear import mechanisms of human APOBEC3B and AID.
Li, M., S.M. Shandilya, M.A. Carpenter, A. Rathore, W.L. Brown, A.L. Perkins, D.A. Harki, J. Solberg, D.J. Hook, K.K. Pandey, M.A. Parniak, J.R. Johnson, N.J. Krogan, M. Somasundaran, A. Ali, C.A. Schiffer, & R.S. Harris (2012) First-In-Class Small Molecule Inhibitors of the Single-Strand DNA Cytosine Deaminase APOBEC3G. ACS Chemical Biology, 7, 506-517.
›Brief description: This paper reports a high throughput screen for inhibitors of the cytosine deaminase APOBEC3G. The activity and mechanism-of-action of several first-in-class inhibitors are detailed.
Hultquist, J.F., M. Binka, R.S. LaRue, V. Simon, & R.S. Harris. (2012) Vif Proteins of Human and Simian Immunodeficiency Viruses Require Cellular CBFβ to Degrade APOBEC3 Restriction Factors. Journal of Virology, 86, 2874-2877.
›Brief description: This paper demonstrates that the cellular transcription factor CBFβ is hijacked by Vif proteins from multiple HIV subtypes and is essential for the neutralization of all Vif-sensitive APOBEC3 proteins.
Jäger, S., D.Y. Kim, J.F. Hultquist, K. Shindo, R.S. LaRue, E. Kwon, M. Li, B.D. Anderson, L. Yen, D. Stanley, C. Mahon, J. Kane, K. Franks-Skiba, P. Cimermancic, A. Burlingame, A. Sali, C.S. Craik, R.S. Harris, J.D. Gross, & N.J. Krogan. (2012) Vif hijacks CBFβ to degrade APOBEC3G and promote HIV-1 infection. Nature, 481, 371-375.
›Brief description: This landmark paper reports on a new HIV dependency factor, the cellular transcription factor CBFβ, that HIV Vif requires to assemble an E3 ubiquitin ligase complex and neutralize the antiviral restriction factor, APOBEC3G.
›Brief description: This paper reports on the HIV-1 restriction activity of the full human and rhesus APOBEC3 repertoires in T cells.
›Brief description: This paper reports on a single amino acid residue in APOBEC3F that is crucial for its susceptibility to HIV-1 Vif. Mutation of this residue inhibits Vif-mediated APOBEC3F degradation.
Refsland, E.W., M.D. Stenglein, K. Shindo, J.S. Albin, W.L. Brown & R.S. Harris (2010) Quantitative profiling of the full APOBEC3 mRNA repertoire in lymphocytes and tissues: implications for HIV-1 restriction. Nucleic Acids Research, 38, 4274-84.
›Brief description: This paper reports a panel of qPCR assays for the specific detection of each human APOBEC3 mRNA and includes expression profiling of several cell commonly used lines and tissue types.
LaRue, R.S., J. Lengyel, S.R. Jónsson, V. Andrésdóttir & R.S. Harris (2010) Lentiviral Vif degrades the APOBEC3Z3/APOBEC3H protein of its mammalian host and is capable of cross-species activity. Journal of Virology, 84, 8193-8201.
›Brief description: This paper is the first to show degradation of multiple species' APOBEC3H orthologues by their host-specific lentiviral Vif and the capacity of some of these Vif proteins to neutralize APOBEC3s of other species.
Albin, J.S. and R.S. Harris (2010) Interactions of host APOBEC3 restriction factors with HIV-1 in vivo: implications for therapeutics. Expert Reviews in Molecular Medicine, 12:e4, 1-26.
›Brief description:This paper has been published by Expert Reviews in Molecular Medicine and is available at the journal website (© Cambridge University Press 2010): PDF
Stenglein, M.D., M.B. Burns, M. Li, J. Lengyel & R.S. Harris (2010) APOBEC3 proteins mediate the clearance of foreign DNA from human cells. Nature Structure and Molecular Biology, 17(2), 222-229. Epub 2010 Jan 10.
›Brief description: This paper is the first to describe APOBEC3 proteins as foreign DNA restriction factors, with net activities analogous to those of bacterial restriction endonucleases.
Shandilya, S.M.D., M.N.L. Nalam, E.A. Nalivaika, P.J. Gross, J.C. Valesano, K. Shindo, M. Li, M. Munson, E. Harjes, T. Kouno, H. Matsuo, R.S. Harris, M. Somasundaran & C.A. Schiffer (2010) Crystal structure of the APOBEC3G catalytic domain reveals potential oligomerization interfaces. Structure, 18(1), 28-38.
›Brief description: This paper reports the highest resolution structure to-date of the APOBEC3G catalytic domain, a prototype for understanding all other DNA cytidine deaminases.
›Brief description: This paper describes the first high-resolution structure of the APOBEC3G catalytic domain.
Haché, G., K. Shindo, J.S. Albin & R.S. Harris (2008) Evolution of HIV-1 isolates that use a novel Vif-independent mechanism to resist restriction by human APOBEC3G. Current Biology, 18, 819-824.
›Brief description: The paper describes the evolution of novel HIV-1 isolates that resist APOBEC3G by a novel Vif-independent tolerance mechanism.
Stenglein, M.D. & R.S. Harris (2006) APOBEC3B and APOBEC3F inhibit L1 retrotransposition by a DNA deamination-independent mechanism. Journal of Biological Chemistry, 281, 16837-41.
›Brief description: This paper is one of the first to show that APOBEC3 proteins can inhibit the replication of the non-LTR retrotransposon L1.
Schumacher, A.J., D.V. Nissley & R.S. Harris (2005) APOBEC3G hypermutates genomic DNA and inhibits Ty1 retrotransposition in yeast. Proceedings of the National Academy of Sciences USA, 102, 9854-9.
›Brief description: This manuscript showed that APOBE3G was capable of functioning in a heterologous system, inhibiting the replication of the yeast retroelement Ty1 and deaminating yeast genomic DNA.
Liddament, M.T., W.L. Brown, A.J. Schumacher & R.S. Harris (2004) APOBEC3F properties and hypermutation preferences indicate activity against HIV-1 in vivo. Current Biology, 14, 1385-91.
›Brief description: This manuscript demonstrates that APOBEC3F is a potent HIV-1 restriction factor that is counteracted by Vif.
Harris*, R.S., K.N. Bishop*, A.M. Sheehy, H.M. Craig, S.K. Petersen-Mahrt, I.N. Watt, M.S. Neuberger & M.H. Malim (2003) DNA deamination mediates innate immunity to retroviral infection. Cell, 113, 803-9.
›Brief description: This paper demonstrates that APOBEC3G is a potent retrovirus restriction factor that deaminates cDNA cytosines to uracils and causes genomic strand G-to-A hypermutations.
Harris*, R.S., S.K. Petersen-Mahrt* & M.S. Neuberger (2002) RNA editing protein APOBEC1 and some of its homologues can act as DNA mutators. Molecular Cell, 10, 1247-53.
›Brief description: This paper is the first to show that APOBEC3G deaminates DNA cytosines to uracils and that the well known RNA editing protein APOBEC1 can also edit DNA.
Petersen-Mahrt*, S.K., R.S. Harris* & M.S. Neuberger (2002) AID mutates E. coli suggesting a DNA deamination mechanism for antibody diversification. Nature, 418, 99-103.
›Brief description: This manuscript is the first to show that AID catalyzes DNA cytosine to uracil deamination, a major result that prompted a DNA deamination model for antibody gene diversification in vertebrates.
Harris, R.S., S. Longerich & S.M. Rosenberg (1994) Recombination in adaptive mutation. Science, 264, 258-60.
›Brief description: This paper revealed that stationary-phase lac reversion in E. coli is dependent on the RecA and RecBCD recombinase proteins.