006 Hurtig Hall
tel:617.373.2865
fax: 617.373.8795
   email: p.beuning@neu.edu

Dr. Beuning's web site

Chemical Biology and Biotechnology

Education

2000 Ph.D. University of Minnesota

1994 B.A. Macalester College, St. Paul, Minnesota

Honors & Awards

Research Interests

The interests of Prof. Beuning’s lab are to understand cellular responses to genotoxic stress. All organisms experience damage to their genetic material from environmental and endogenous sources. Multiple redundant systems exist to identify and remove damaged bases from DNA in organisms from bacteria to humans. For example, the bacterial SOS response, involving the upregulation of at least 40 genes in E. coli, is induced when cells experience damage to their DNA and other stresses. Many of the genes induced as part of the SOS response are

responsible for DNA repair and cell cycle regulation. Another group of genes induced as part of the SOS response play a role in tolerance to DNA damaging agents at a potentially mutagenic cost.

The Y family DNA polymerases are specialized DNA polymerases that are able to replicate a wide array of damaged DNA substrates, including thymine-thymine dimers, nucleotide base adducts, and abasic sites. The presence of Y family polymerases in cells confers resistance to several classes of DNA damaging agents and environmental toxins. A major focus of our research is to understand the specificity of these DNA polymerases for their damaged DNA substrates using protein engineering, molecular modeling and chemical synthesis.

A second focus of the lab is on protein rings that encircle DNA. These protein clamps provide for highly processive and efficient DNA replication by tethering DNA polymerases to their DNA substrates. Alternative versions of processivity clamps are found throughout evolution and seem to function in DNA damage tolerance and cell cycle control. Using biochemical, biophysical, and genetic approaches, we are investigating the molecular mechanisms by which alternative processivity clamp proteins confer resistance to DNA damage, and their possible roles in DNA replication.

 Selected Publications 

Micah J. McCauley, Leila Shokri, Jana Sefcikova, Česlovas Venclovas, Penny J. Beuning, and Mark C. Williams (2008) “Distinct Double- and Single-Stranded DNA Binding of E. coliReplicative DNA Polymerase III Alpha Subunit” ACS Chemical Biology 3 577-587.

Jarosz, Daniel F.; Beuning, Penny J.; Cohen, Susan E.; Walker, Graham C. Y-family DNA polymerases in Escherichia coli. Trends in Microbiology (2007), 15(2), 70-77.

Cruceanu, Margareta; Stephen, Andrew G.; Beuning, Penny J.; Gorelick, Robert J.; Fisher, Robert J.; Williams, Mark C. Single DNA molecule stretching measures the activity of chemicals that target the HIV-1 nucleocapsid protein. Analytical Biochemistry (2006), 358(2), 159-170.

Beuning, Penny J.; Simon, Sharotka M.; Zemla, Adam; Barsky, Daniel; Walker, Graham C. A Non-cleavable UmuD Variant That Acts as a UmuD' Mimic. Journal of Biological Chemistry (2006), 281(14), 9633-9640.