Paul Doetsch, Ph.D.
Senior Investigator
Genome Integrity and Structural Biology Laboratory / Mutagenesis and DNA Repair Regulation Group
NIEHS
Research Topics
The group’s major areas of research are the regulation of DNA repair and the interaction of the replication and transcription machinery with DNA damage. DNA repair studies are primarily focused on the base excision repair (BER) pathway and include the genetic and biological consequences, including tumorigenesis, dysregulation, as well as interactions of BER components with other repair systems. The group’s studies on the effects of various types of DNA damage on RNA polymerases led to the discovery of transcriptional mutagenesis (TM) several decades ago. The research established that TM occurs in bacterial and mammalian cells.
If a phenotype caused by TM results in DNA replication or cell cycle entry, one of the resulting daughter cells may acquire a permanent DNA mutation, and thus permanent establishment of the phenotype. This mechanism has been termed retromutagenesis (RM). TM and RM may have a deleterious impact on human health by contributing to the etiology of diseases, such as cancer, as well as giving rise to antibiotic-resistant pathogenic bacteria. The group is also conducting studies on the mutational signatures caused by redox stress in specialized DNA contexts and environments.
Biography
Doetsch received a B.S. in biochemistry from the University of Maryland, an M.S. in medicinal chemistry and pharmacognosy from Purdue University, and a Ph.D. in biochemistry from Temple University. Following postdoctoral training at the Dana Farber Cancer Institute and Harvard Medical School, he served on the faculty of Emory University School of Medicine for 32 years, led a DNA repair and mutagenesis research group, and held various leadership positions including Associate Director for Basic Research (2005-2017) of the Winship Cancer Institute. He joined NIEHS January 2018.
Selected Publications
- Degtyareva NP, Saini N, Sterling JF, Placentra VC, Klimczak LJ, Gordenin DA, Doetsch PW. Mutational signatures of redox stress in yeast single-strand DNA and of aging in human mitochondrial DNA share a common feature. PLoS Biol. 2019;17(5):e3000263.
- Limpose KL, Trego KS, Li Z, Leung SW, Sarker AH, Shah JA, Ramalingam SS, Werner EM, Dynan WS, Cooper PK, Corbett AH, Doetsch PW. Overexpression of the base excision repair NTHL1 glycosylase causes genomic instability and early cellular hallmarks of cancer. Nucleic Acids Res. 2018;46(9):4515-4532.
- Degtyareva NP, Placentra VC, Gabel SA, Klimczak LJ, Gordenin DA, Wagner BA, Buettner GR, Mueller GA, Smirnova TI, Doetsch PW. Changes in metabolic landscapes shape divergent but distinct mutational signatures and cytotoxic consequences of redox stress. Nucleic Acids Res. 2023;51(10):5056-5072.
- Kar A, Degtyareva NP, Doetsch PW. Human NTHL1 expression and subcellular distribution determines cisplatin sensitivity in human lung epithelial and non-small cell lung cancer cells. NAR Cancer. 2024;6(1):zcae006.
- García-Villada L, Degtyareva NP, Brooks AM, Goldberg JB, Doetsch PW. A role for the stringent response in ciprofloxacin resistance in Pseudomonas aeruginosa. Sci Rep. 2024;14(1):8598.
Related Scientific Focus Areas
Molecular Biology and Biochemistry
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Microbiology and Infectious Diseases
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This page was last updated on Thursday, January 31, 2019