Biochemistry, Molecular Biology and Biophysics

Reuben S. Harris

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Research Interests

Mechanisms of purposeful mutation relating to innate and adaptive immunity

Lab Web Site

Research Description

Our laboratory is interested in mutations, not only their roles in human cancers but also how these processes can be harnessed to destroy pathogens. While mutation is often thought of in a negative context, mutations at the DNA level can also be protective and beneficial. In the past three years, our research has been instrumental in the discovery of two fundamental mutation-generating mechanisms. In each, the purposeful use of mutation governs a potent pathogen defense. One mechanism protects our cells from retroviruses such as HIV-1, and the other helps strengthen our antibodies such that an effective immune response occurs when we are infected. The common link between these important immune defenses systems is that they are underpinned by related human proteins that use identical strategies --- the chemical conversion of the DNA base cytosine into uracil.

Recent Publications

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. (pubmed)

Chen, K.-M., E. Harjes, P.J. Gross, A. Fahmy, Y. Lu, K. Shindo, R.S. Harris# & H. Matsuo# (2008) Structure of the DNA deaminase domain of the HIV-1 restriction factor APOBEC3G, Nature, 452, 116-119 (# correspondence).(pubmed)

Schumacher, A.J., G. Haché, D.A. MacDuff, W.L. Brown & R.S. Harris (2008) The DNA deaminase activity of human APOBEC3G is required for Ty1, MusD and HIV-1 restriction. Journal of Virology, 82, 2652-60 (pubmed)

Chen, K.-M., N.A. Martemyanova, Y. Lu, H. Matsuo# & R.S. Harris# (2007) A structural model of the DNA deaminase domain of APOBEC3G corroborated by extensive mutagenesis experiments. FEBS Letters, 581, 4761-66 (# correspondence). (pubmed)

Jónsson, S.R., R.S. LaRue, M.D. Stenglein, S.C. Fahrenkrug, V. Andrésdóttir & R.S. Harris (2007) The restriction of zoonotic PERV transmissions by human APOBEC3G. PLoS One, 2(9), e893 (8 pages). doi:10.1371/journal.pone.0000893 (pubmed)

Stenglein, M.D. & R.S. Harris (2006) APOBEC3B and APOBEC3F inhibit L1 retrotranspostion by a DNA deamination-independent mechanism. Journal of Biological Chemistry, 281, 16837-41. (pubmed)

Jónsson, S.R., G. Haché, M.D. Stenglein, S.C. Fahrenkrug, V. Andrésdóttir & R.S. Harris (2006) Evolutionarily conserved and non-conserved retrovirus restriction activities of artiodactyl APOBEC3F proteins. Nucleic Acids Research, 34, 5683-94. (pubmed)

MacDuff, D.A., M.S. Neuberger & RS Harris (2006) MDM2 can interact with the C-terminus of AID but it is inessential for antibody diversification in DT40 B cells. Molecular Immunology, 43, 1099-108. (pubmed)

Schumacher, A.J., D.V. Nissley & RS Harris (2005) APOBEC3G hypermutates genomic DNA and inhibits Ty1 retrotransposition in yeast. Proceedings of the National Academy of Sciences USA, 102, 9854-9859. (pubmed)

Haché, G, M.T. Liddament & RS Harris (2005) The retroviral hypermutation specificity of APOBEC3F and APOBEC3G is governed by the C-terminal DNA cytosine deaminase domain. Journal of Biological Chemistry, 280, 10920-10924. (pubmed)

Liddament, M. T., Brown, W. L., Schumacher, A. J., and Harris, R. S. (2004). APOBEC3F properties and hypermutation preferences indicate activity against HIV-1 in vivo. Curr Biol 14, 1385-1391. (pubmed)

Beale, R. C., Petersen-Mahrt, S. K., Watt, I. N., Harris, R. S., Rada, C., and Neuberger, M. S. (2004). Comparison of the differential context-dependence of DNA deamination by APOBEC enzymes: correlation with mutation spectra in vivo. J Mol Biol 337, 585-596. (pubmed)

Conticello, S. G., Harris, R. S., and Neuberger, M. S. (2003). The Vif protein of HIV triggers degradation of the human antiretroviral DNA deaminase APOBEC3G. Curr Biol 13, 2009-2013. (pubmed)

Harris, R. S., Bishop, K. N., Sheehy, A. M., Craig, H. M., Petersen-Mahrt, S. K., Watt, I. N., Neuberger, M. S., and Malim, M. H. (2003). DNA deamination mediates innate immunity to retroviral infection. Cell 113, 803-809. (pubmed)

Harris, R. S., Petersen-Mahrt, S. K., and Neuberger, M. S. (2002). RNA editing enzyme APOBEC1 and some of its homologs can act as DNA mutators. Molecular Cell 10, 1247-1253. (pubmed)

Petersen-Mahrt, S. K., Harris, R. S., and Neuberger, M. S. (2002). AID mutates E. coli suggesting a DNA deamination mechanism for antibody diversification. Nature 418, 99-103. (pubmed)

Harris, R. S., Sale, J. E., Petersen-Mahrt, S. K., and Neuberger, M. S. (2002). AID is essential for immunoglobulin V gene conversion in a cultured B cell line. Current Biology 12, 435-438. (pubmed)