Lorena S. Beese
Lorena S. Beese
Lorena Sue Beese
|Residence||Durham, North Carolina|
|Fields||Cancer Research, DNA replication, DNA mismatch repair|
|Institutions||Duke University School of Medicine|
Lorena Beese is a James B. Duke Professor of Biochemistry at Duke University. She received her PhD in Biophysics from Brandeis University and did her postdoctoral work with Dr. Thomas A. Steitz at Yale University. In 2009 Dr. Beese was elected to the National Academy of Sciences. Her research interests include structural biochemistry of DNA replication and human DNA mismatch repair and its connection to carcinogenesis. She is also interested in protein prenylation enzymes as targets for structure-based discovery of anticancer therapeutics and re-purposing of such therapeutics to treat pathogenic fungi and malaria.
- Signal transduction
- Structure based drug design
- DNA replication
- DNA mismatch repair
- Observing enzymes in action
In 2008, Beese published her research on Candida albicans' geranylgeranyltransferase-1 (GGTase-1) protein structure. Candida albican is an opportunistic pathogen commonly found in the human microbiota. In immune compromised individual, C. albicans result in infections that display resistance to anti-fungal therapies. The investigation and discovery of the structure of an GGTases-1 of Candida albicans provides more information for scientists to understand the protein’s importance in the survival of the pathogen and suggests its’ potential to be targeted for disease treatment. 
While at Duke University in 2011, Beese, along with her colleague Eugene Wu, investigated the structural adaptation of DNA Polymerase observed during the recognition and correction of incorrect base pairing. Her findings included an intermediate state between the characteristic “open” and “closed” states of polymerase during DNA replication. This intermediary was termed the “Ajar” confirmation. Beese found that inserting an incorrect nucleotide into the growing DNA caused a bend in the helicase of the DNA polymerase. This finding suggests a mechanism by which polymerases are able to detect incorrect base pairing. 
Beese had an integral role in identifying the mismatch repair mechanism through which hExo1 identifies DNA damage. In order to maintain the integrity of DNA, enzymes such as Human exonuclease 1 (hExo1) repair damages in DNA. Through her research, Beese found that the hExo1 enzyme binds the DNA near the site of mismatched pairing, and through exonuclease and endonuclease activity, the enzyme is able to assist in the identification and replacement of incorrect base pairs. 
- Orans, J. McSweeney; Iyer, R.R.; Hast, M.A.; Hellinga, H.W.; Modrich, P.; Beese, L.S. (2011). "Structure of human exonuclease 1 DNA complexes suggest a unified mechanism for nuclease family". Cell. 145 (2): 212–223. doi:10.1016/j.cell.2011.03.005. PMC 3093132. PMID 21496642.
- Wu, E.Y.; Beese, L.S. (2011). "The structure of a high fidelity DNA polymerase bound to a mismatched nucleotide reveals an ajar intermediate conformation in the nucleotide selection mechanism". J Biol Chem. 286: 19758–67. doi:10.1074/jbc.M110.191130. PMC 3103354. PMID 21454515.
- Hast, M.A.; Fletcher, S.; Cummings, C.G.; Pusateri, E.E.; Blaskovich, M.A.; Rivas, K.; Gelb, M.H.; Van Voorhis, C.V.; Sebti, S.M.; Hamilton, A.D.; Beese, L.S. (2009). "Structural basis for binding and selectivity of antimalarial and anticancer ethylenediamine inhibitors to protein farnesyltransferase". Chemistry & Biology. 16: 181–192. doi:10.1016/j.chembiol.2009.01.014. PMC 2671474. PMID 19246009.
- Hast, M.A.; Beese, L.S. (2008). "Structure of protein geranylgeranyltransferase-I from the human pathogen Candida albicans complexed with a lipid substrate". J Biol Chem. 283 (46): 31933–40. doi:10.1074/jbc.M805330200. PMC 2581548. PMID 18713740.
- Warren, JJ; Pohlhaus, TJ; Changela, A; Iyer, RR; Modrich, PL; Beese, LS (2007). "Structure of the human MutSalpha DNA lesion recognition complex". Mol Cell. 26 (4): 579–92. doi:10.1016/j.molcel.2007.04.018.
- Warren, J.J.; Forsberg, L.J.; Beese, L.S. (2006). "The structural basis for the mutagenicity of O6-methyl-guanine lesions". Proc. Natl. Acad. Sci. USA. 103 (52): 19701–6. doi:10.1073/pnas.0609580103. PMC 1750904.
- Terry, K.L.; Casey, P.J.; Beese, L.S. (2006). "Conversion of protein farnesyltransferase to a geranylgeranyltransferase". Biochemistry. 45 (32): 9746–55. doi:10.1021/bi060295e. PMID 16893176.
- Lane, K.T.; Beese, L.S. (2006). "Thematic review series: lipid posttranslational modifications. Structural biology of protein farnesyltransferase and geranylgeranyltransferase type I.". Journal of Lipid Research. 47 (4): 681–699. doi:10.1194/jlr.r600002-jlr200. PMID 16477080.
- Beese, L., & Harvard University. (2005). Structure and mechanism of protein prenyltransferases: Analysis of a cancer therapeutic target.
- Beese, L., & Harvard University. (2005). Structures and mechanisms of a DNA polymerase: Nature's copier and spellchecker in action.
- Johnson, S.J.; Beese, L.S. (2004). "Structures of mismatch replication errors observed in a DNA polymerase". Cell. 116: 803–816. doi:10.1016/s0092-8674(04)00252-1. PMID 15035983.
- Hsu, G.W.; Ober, M.; Carell, T.; Beese, L.S. (2004). "Error-prone replication of oxidatively damaged DNA by a high-fidelity DNA polymerase". Nature. 431 (7005): 217–21. doi:10.1038/nature02908. PMID 15322558.
- Johnson, S.J.; Taylor, J.S.; Beese, L.S. (2003). "Processive DNA synthesis observed in a polymerase crystal suggests a mechanism for the prevention of frameshift mutations". Proc. Natl. Acad. Sci. USA. 100 (7): 3895–3900. doi:10.1073/pnas.0630532100. PMC 153019. PMID 12649320.
- Taylor, J.S.; Reid, T.S.; Terry, K.L.; Casey, P.J.; Beese, L.S. (2003). "Structure of mammalian protein geranylgeranyltransferase type-1". EMBO J. 22 (22): 5963–5974. doi:10.1093/emboj/cdg571. PMC 275430. PMID 14609943.
- Long, SB; Casey, P.; Beese, LS (2002). "The reaction path of protein farnesyltransferase at atomic resolution". Nature. 419 (6907): 645–50. doi:10.1038/nature00986. PMID 12374986.
- Long, SB; Hancock, PJ; Kral, AM; Hellinga, HW; Beese, LS (2001). "The crystal structure of human protein farnesyltransferase reveals the basis for inhibition by CaaX tetrapeptides and their mimetics". Proc Natl Acad Sci U S A. 98 (23): 12948–53. doi:10.1073/pnas.241407898. PMC 60805. PMID 11687658.
- Kiefer, J. R.; Mao, C.; Braman, J. C.; Beese, L. S. (1998). "Visualizing DNA replication in a catalytically active Bacillus DNA polymerase crystal [see comments]". Nature. 6664: 304–7.
- "Lorena Beese, Member Directory". National Academy of Sciences. Retrieved 30 March 2016.
- "Lorena S. Beese (Primary)". Biochemistry Lab, Duke University School of Medicine. Retrieved 30 March 2016.
- Hast, Michael A.; Beese, Lorena S. (2008-08-19). "Structure of Protein Geranylgeranyltransferase-I from the Human PathogenCandida albicansComplexed with a Lipid Substrate". Journal of Biological Chemistry. 283 (46): 31933–31940. doi:10.1074/jbc.m805330200. ISSN 0021-9258.
- Nobile, Clarissa J.; Johnson, Alexander D. (2015-10-15). "Candida albicansBiofilms and Human Disease". Annual Review of Microbiology. 69 (1): 71–92. doi:10.1146/annurev-micro-091014-104330. ISSN 0066-4227.
- Wu, Eugene Y.; Beese, Lorena S. (2011-03-19). "The Structure of a High Fidelity DNA Polymerase Bound to a Mismatched Nucleotide Reveals an "Ajar" Intermediate Conformation in the Nucleotide Selection Mechanism". Journal of Biological Chemistry. 286 (22): 19758–19767. doi:10.1074/jbc.m110.191130. ISSN 0021-9258.
- Orans, Jillian; McSweeney, Elizabeth A.; Iyer, Ravi R.; Hast, Michael A.; Hellinga, Homme W.; Modrich, Paul; Beese, Lorena S. (2011-04). "Structures of Human Exonuclease 1 DNA Complexes Suggest a Unified Mechanism for Nuclease Family". Cell. 145 (2): 212–223. doi:10.1016/j.cell.2011.03.005. ISSN 0092-8674. Check date values in: