DNA Replication and Repair

Among the macromolecules in the cell, DNA is the only macromolecule for which mechanisms exist to ensure its integrity. DNA polymerases are responsible for the actual duplication of the DNA genome, but many other proteins serve critical roles. Several research groups at MSU study the mechanics of DNA synthesis, including proof-reading and the role of proteins that prevent single-stranded DNA from forming hairpins. .Newly discovered DNA polymerases have been shown to participate in repairing specific types of DNA damage caused by different classes of mutagens. Molecular and cellular processes of DNA repair, and the involvement of DNA recombination in maintaining the integrity of DNA, have been examined with both in vivo and in vitro methods. Included here are transcription factors that mediate the cellular response to mutagens found in the environment. The impact of mutagens on DNA integrity is also an interest of research groups investigating the genetics of cancer.

Another topic of inquiry is the regulation of DNA replication. Since the process is coordinated with cell growth and division, a suite of proteins must be coordinately regulated to accomplish precise control, with cellular origins being fired once and only once during the cell cycle. In contrast, cancer cells may experience genome amplification, leading to failure of chemotherapy and oncogenic progression. The mechanism of gene amplification in cancer cells is studied in the laboratory with a virally encoded oncoprotein, which controls the multiple firing of the viral origin.

Several model systems are used to examine the processes of DNA replication, mutation, and repair. The replication of linear DNA is studied in fungal mitochondrial plasmids and yeast chromosomes, where two very different enzymes function: the former utilizes a bacteriophage-type polymerase and protein priming, while the latter relies upon telomerase. Other research programs utilize mutators that have elevated rates of mutation serve as genetic tools to learn about components that contribute to high fidelity maintenance of the genomes of bacteria and chloroplasts. A great diversity in approaches, methodology, and organisms are available at MSU to the student interested in studying the genetics of DNA replication and repair.