Roeland M. Schaaper, Ph.D.
Genome Integrity & Structural Biology Laboratory / Mechanisms of Mutation Group
Building 101, Room E348B
111 T.W. Alexander Drive
Research Triangle Park, NC 27709
We study the multiple mechanisms by which cells undergo mutation. In effect, this is a detailed investigation into the broad range of genetic and enzymatic mechanisms by which cells try to avoid making mutations. We use as model system the bacterium Escherichia coli, employing genetic and biochemical approaches. We study both mutator (elevated mutation rates) and antimutator (reduced mutation rates) organisms. The study of mutators provides insights into the operative mutation prevention systems, while the study of antimutators provides insight into the actual sources of mutations [such as errors of DNA replication, DNA repair errors, unrepaired DNA damages, or altered DNA precursor pools (dNTPs)]. Specifically, our lab investigates: (i) the fidelity of the multi-subunit DNA replication complex responsible for the simultaneous replication of leading and lagging strands, including the role played by individual subunits of this complex, (ii) the role of the accessory DNA polymerases in chromosomal replication, (iii) the role of the deoxynucleoside triphosphate DNA precursors (dNTPs) in determining in vivo replication error rates, (iv) the mechanisms used to maintain "clean" cellular dNTP pools by removing mutagenic and toxic derivatives (pool sanitation), and (v) novel molybdenum-cofactor-dependent activities that we have discovered in E. coli that detoxify N-hydroxylated base analogs and related chemical compounds.
Dr. Schaaper obtained a Masters of Engineering degree from Delft University of Technology, The Netherlands, in 1977. He did his graduate studies at the University of Leiden with Dr. Barry W. Glickman, and at the University of Washington with Dr. Lawrence A. Loeb. He obtained his Ph.D. in Mathematics and Natural Sciences from the University of Leiden in 1982. He then joined the Laboratory of Molecular Genetics at the National Institute of Environmental Health Sciences (NIEHS) as a Postdoctoral Fellow with Dr. Barry Glickman, working on the mechanisms of mutagenesis. He became a principal investigator in the Laboratory of Molecular Genetics at the NIEHS in 1987, continuing his studies of the molecular mechanisms of mutagenesis.
Maslowska KH, Makiela-Dzbenska K, Fijalkowska IJ, Schaaper RM. Suppression of the E. coli SOS response by dNTP pool changes. Nucleic Acids Res. 2015;43(8):4109-20.
Gawel D, Hamilton MD, Schaaper RM. A novel mutator of Escherichia coli carrying a defect in the dgt gene, encoding a dGTP triphosphohydrolase. J Bacteriol. 2008;190(21):6931-9.
Ahluwalia D, Bienstock RJ, Schaaper RM. Novel mutator mutants of E. coli nrdAB ribonucleotide reductase: insight into allosteric regulation and control of mutation rates. DNA Repair (Amst). 2012;11(5):480-7.
Fijalkowska IJ, Schaaper RM, Jonczyk P. DNA replication fidelity in Escherichia coli: a multi-DNA polymerase affair. FEMS Microbiol Rev. 2012;36(6):1105-21.
Singh D, Gawel D, Itsko M, Hochkoeppler A, Krahn JM, London RE, Schaaper RM. Structure of Escherichia coli dGTP triphosphohydrolase: a hexameric enzyme with DNA effector molecules. J Biol Chem. 2015;290(16):10418-29.