The CSC grant program seeks to establish or improve research collaborations between “R1 Doctoral Universities” (that conduct high levels of research activity) and “PUIs,” or primarily undergraduate institutions. These collaborations strengthen the research environments at PUIs, expose graduate students to possible careers at PUIs, and enhance the experience of undergraduate students as they consider further study.
With the grant, Dr. Sampoli Benitez and Dr. Beuning will receive $3,000 in funding toward their collaborative project. In addition, Dr. Sampoli Benitez will travel to Northeastern to present on her research and her career at a PUI, graduate students from Northeastern will visit MMC to talk to undergraduates about applying to graduate school, and MMC students may have the opportunity to go to Northeastern to collaborate on the research project.
The goal of the project is to understand how the conformational changes in damage-bypass DNA polymerases correlate with their catalytic activity. The Y family DNA polymerases are specialized to copy damaged DNA, which allows cells to tolerate DNA damage without repairing the damage. The damage that remains in the DNA can subsequently be repaired by canonical DNA repair processes. The Beuning laboratory has previously shown that Y-family DNA polymerases undergo specific, substrate-induced conformational changes only when in the presence of preferred substrates. In order to probe the roles of individual amino acids in this conformational change, the Beuning and Sampoli Benitez laboratories are partnering to couple molecular dynamics (MD) simulations with experimental results. The Sampoli Benitez group has extensive experience in molecular dynamics simulations of DNA polymerases. The Sampoli Benitez group will carry out molecular dynamics simulations of the Y-family DNA polymerases E. coli DinB and human DNA polymerase kappa (polk). The MD simulations are expected to reveal the atomic level details of the protein dynamics upon binding damaged DNA and either the correct or incorrect incoming nucleotide. We expect this work to generate testable hypotheses about the protein dynamics and the protein-nucleic acid interactions that regulate polymerase activity.