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October 2011


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Cavanaugh and Wilson group paper highlighted by JBC

By Eddy Ball
October 2011

Nisha Cavanaugh, Ph.D.

Along with her research in structural biology, Cavanaugh is a member of the NIEHS Trainees Assembly Steering Committee. (Photo courtesy of Steve McCaw)

The Sept. 9 issue of the Journal of Biological Chemistry (JBC) showcases the issue's paper of the week, from the NIEHS DNA Repair and Nucleic Acid Enzymology Group(http://www.niehs.nih.gov/research/atniehs/labs/lsb/dnarna/staff.cfm), with a cover illustration featuring an x-ray crystallographic image from the paper and a profile(http://www.jbc.org/content/286/36/e99965/suppl/DCAuthor_profile) Exit NIEHS of its first author, postdoctoral fellow Nisha Cavanaugh, Ph.D.

JBC associate editors and editorial board members bestow the honor of paper of the week(http://www.jbc.org/potw) Exit NIEHS to the top one percent of papers reviewed in terms of significance and overall importance, according to the JBC website. JBC is the most cited journal in biomedical research, publishing some 38,000 pages of new research each year as well as enjoying an impact factor of 5.328 and the highest overall importance eigenfactor score(http://admin-apps.webofknowledge.com/JCR/help/h_eigenfact.htm) Exit NIEHS of any journal in its category.

A multifaceted approach

The DNA Repair and Nucleic Acid Enzymology Group is headed by senior researcher Samuel Wilson, M.D.(http://www.niehs.nih.gov/research/atniehs/labs/lsb/dnarna/index.cfm), who was lead researcher on the paper (see story(http://www.niehs.nih.gov/news/newsletter/2011/august/science-ribonucleotide/index.cfm)), and is part of the NIEHS Laboratory of Structural Biology (LSB). As Wilson explained, the study resulted from a multifaceted approach toward understanding the enzyme DNA polymerase (pol) beta that involved a collaborative effort between members of his own group - William Beard, Ph.D., Vinod Batra, Ph.D., Cavanaugh, and David Shock - and members of the LSB Computational Chemistry and Molecular Modeling Group - head Lee Pedersen, Ph.D., and Lalith Perera, Ph.D.

In the JBC author profile, Cavanaugh pointed to the primary components of the team's approach, stating, “In this study, we build on our previous work and use four different methods - site-directed mutagenesis, kinetics, x-ray crystallography, and computational modeling - to examine how pol beta excludes ribonucleotides from its active site.”

In the course of her scientific training at the University of Colorado at Boulder and NIEHS, Cavanaugh has been a coauthor on eight peer-reviewed publications, four of them since joining the Wilson group in 2009. Three of them have appeared in JBC, another four were published in Biochemistry, and one appeared in Cellular and Molecular Life Sciences.

Citation: Cavanaugh NA, Beard WA, Batra VK, Perera L, Pedersen LG, Wilson SH(http://www.ncbi.nlm.nih.gov/pubmed/21733843) Exit NIEHS. 2011. Molecular insights into DNA polymerase deterrents for ribonucleotide insertion. J Biol Chem 286(36):31650-31660.

Samuel Wilson, M.D.

In his roles as a leader and researcher at NIEHS, Wilson has long championed research on the role of DNA pol beta in DNA repair and replication. (Photo courtesy of Steve McCaw)

crystal structure of DNA polymerase

The cover image for JBC issue shows a crystal structure of DNA polymerase beta bound with gapped DNA and a ribonucleoside triphosphate. The structure reveals that ribonucleotides are accommodated in the active site. DNA pol beta employs two strategies, steric and geometric, with a single protein residue to deter ribonucleotide insertion. (Image courtesy of the NIEHS DNA Repair and Nucleic Acid Enzymology Group and JBC)



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