Roel Schaaper, Ph.D.
Genome Integrity & Structural Biology Laboratory / Mechanisms of Mutation Group
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.
- Klemm BP, Singh D, Smith CE, Hsu AL, Dillard LB, Krahn JM, London RE, Mueller GA, Borgnia MJ, Schaaper RM. Mechanism by which T7 bacteriophage protein Gp1.2 inhibits Escherichia coli dGTPase. Proc Natl Acad Sci U S A. 2022;119(37):e2123092119.
- Klemm BP, Sikkema AP, Hsu AL, Horng JC, Hall TMT, Borgnia MJ, Schaaper RM. High-resolution structures of the SAMHD1 dGTPase homolog from Leeuwenhoekiella blandensis reveal a novel mechanism of allosteric activation by dATP. J Biol Chem. 2022;298(7):102073.
- Maslowska KH, Makiela-Dzbenska K, Mo JY, Fijalkowska IJ, Schaaper RM. High-accuracy lagging-strand DNA replication mediated by DNA polymerase dissociation. Proc Natl Acad Sci U S A. 2018;115(16):4212-4217.
- Bhawsinghka N, Burkholder A, Schaaper RM. Detection of DNA replication errors and 8-oxo-dGTP-mediated mutations in E. coli by Duplex DNA Sequencing. DNA Repair (Amst). 2023;123:103462.
- 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.
Related Scientific Focus Areas
Genetics and Genomics
Molecular Biology and Biochemistry
This page was last updated on Friday, April 12, 2013