Paul Doetsch, Ph.D.

Senior Investigator

Genome Integrity and Structural Biology Laboratory / Mutagenesis and DNA Repair Regulation Group

NIEHS

A218 Rall Building
111 T W Alexander Dr
Research Triangle Park, NC 27709

984-287-3643

paul.doetsch@nih.gov

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

  1. 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.

  2. 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.

  3. Werner E, Alter A, Deng Q, Dammer EB, Wang Y, Yu DS, Duong DM, Seyfried NT, Doetsch PW. Ionizing Radiation induction of cholesterol biosynthesis in Lung tissue. Sci Rep. 2019;9(1):12546.

  4. Chen G, Magis AT, Xu K, Park D, Yu DS, Owonikoko TK, Sica GL, Satola SW, Ramalingam SS, Curran WJ, Doetsch PW, Deng X. Targeting Mcl-1 enhances DNA replication stress sensitivity to cancer therapy. J Clin Invest. 2018;128(1):500-516.

  5. Chen G, Luo Y, Warncke K, Sun Y, Yu DS, Fu H, Behera M, Ramalingam SS, Doetsch PW, Duong DM, Lammers M, Curran WJ, Deng X. Acetylation regulates ribonucleotide reductase activity and cancer cell growth. Nat Commun. 2019;10(1):3213.


This page was last updated on January 31st, 2019