Lorena S. Beese

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Lorena S. Beese
Lorena Sue Beese
ResidenceDurham, North Carolina
Alma mater
Spouse(s)Homme Hellinga
Scientific career
FieldsCancer Research, DNA replication, DNA mismatch repair
InstitutionsDuke 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.[1] 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.[2]

Research Interests[edit]

  • 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.[3] 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.[4] 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.[3]

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.[5]

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.[6]

Selected works[edit]


  1. ^ "Lorena Beese, Member Directory". National Academy of Sciences. Retrieved 30 March 2016.
  2. ^ "Lorena S. Beese (Primary)". Biochemistry Lab, Duke University School of Medicine. Retrieved 30 March 2016.
  3. ^ a b 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. PMC 2581548. PMID 18713740.
  4. ^ 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. PMC 4930275. PMID 26488273.
  5. ^ 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. PMC 3103354. PMID 21454515.
  6. ^ Orans, Jillian; McSweeney, Elizabeth A.; Iyer, Ravi R.; Hast, Michael A.; Hellinga, Homme W.; Modrich, Paul; Beese, Lorena S. (April 2011). "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. PMC 3093132. PMID 21496642.