Biology

BIOL 319 

BIOL 598

Each time a human cell divides billions of base pairs of DNA must be replicated completely, efficiently, and with high fidelity to ensure genomic stability. This requires the coordinated action of hundreds of protein complexes to replicate our DNA as well as recognize and repair DNA damage and mispairing. The inability to fully replicate and repair the DNA can lead to DNA breaks, recombination, deletions, and chromosome rearrangements, which are hallmarks of cancer and many genetic diseases. Our research is focused on gaining a molecular understanding of how these complexes processes are carried out to maintain and protect our genome. Particularly, we focus on the multifunctional, single-stranded DNA binding protein CST. This protein complex is essential in several DNA maintenance pathways, including DNA replication, telomere maintenance, DNA repair and activation of the DNA damage response. Moreover, mutations in CST have been linked to several genetic diseases, pulmonary fibrosis, and cancer. Therefore, our research not only provides important insight into how our genomes are maintained and protected but also how loss of these essential pathways promote human disease. To accomplish our research goals, we use a variety of molecular and cell biology techniques, such as fluorescence microscopy, Western blot, molecular cloning, and flow cytometry.

Ph.D. in Biochemistry 2009 University of Rochester, Rochester, NY

B.S. in Microbiology 2003 Brigham Young University, Provo, UT

Assistant Professor 2023-present Department of Biology, Western Kentucky University, Bowling Green, KY

Assistant Professor 2014-2023 Department of Biological Sciences, University of South Carolina, Columbia, SC

Postdoctoral Fellow 2009-2014 Department of Cancer Biology, University of Cincinnati, Cincinnati, OH

Li, T., Zhang, M., Li, Y., Zhao, R., Han, X., Tang, L., Ma, T., Zhao, X., Zhou, R., Wang, Y., Bai, X., Zhang, K., Geng, X., Sui, L., Feng, X., Zhang, Q., Zhao, Y., Liu, Y.#, Stewart, J.A.#, Wang, F.# (2023) Cooperative interaction of CST and RECQ4 resolves G-quadruplexes and maintains telomere stability. EMBO Reports. In Press doi: 10.15252/embr.202255494

Wang, H., Ma, T., Zhang, X., Chen, W., Lan, Y., Kuang G., Hsu, S.J., He, Z., Chen, Y., Stewart, J., Bhattacharjee, A., Luo, Z., Price, C., Feng, X.# (2023) CTC1 OB-B interaction with TPP1 terminates telomerase and prevents telomere overextension. Nucleic Acids Research. 51:4914-4928 doi: 10.1093/nar/gkad237

Jhanji, M., Rao, C.N., Massey, J.C., Hope M.C., Zhou, X., Keene, C.D., Ma, T., Wyatt, M.D., Stewart, J.A., Sajish, M.# (2022) Cis- and trans-resveratrol have opposite effects on histone serine-ADP-ribosylation and tyrosine induced neurodegeneration. Nature Communications. 13:3244 doi: 10.1038/s41467-022-30785-8

Schuck, P.L.^, Ball, L.E., Stewart, J.A#. (2021) The DNA-binding protein CST associates with cohesin and promotes chromosome cohesion. Journal of Biological Chemistry. 297:101026 doi: 10.1016/j.jbc.2021.101026

Moore, S. #, Patel, R. Stewart, J.A., McLain, A., Heiney, S. (2021) Social inequalities in accelerated aging among southern U.S. women: An analysis of the biosocial and behavioral pathways linking social determinants to telomere length. Biodemography and Social Biology. 66:118-131 doi: 10.1080/19485565.2020.1869918

Ackerson, S. M.^, Gable, C.I.‡, Stewart, J.A#. (2020) Human CTC1 promotes TopBP1 stability and CHK1 phosphorylation in response to telomere dysfunction and global replication stress. Cell Cycle. 19:3491-3507 doi: 10.1080/15384101.2020.1849979

Wang, Y.*, Brady, K.S.*, Caiello, B.P.‡, Ackerson, S.M.^, Stewart, J.A.# (2019) Human CST suppresses origin licensing and promotes AND-1/Ctf4 chromatin association. Life Science Alliance. 2:e201800270 doi: 10.26508/lsa.201800270

Bhattacharjee, A., Stewart, J.A.#, Chaiken, M., Price, C.M.# (2016) STN1 OB fold mutation alters DNA Binding and affects selective aspects of CST function. PLOS Genetics. 12:e1006342 doi: 10.1371/journal.pgen.1006342

Wang, F, Stewart, J.A., Price, C.M.# (2014) Human CST abundance determines recovery from diverse forms of DNA damage and replication stress. Cell Cycle. 13:3488-3498 doi: 10.4161/15384101.2014.964100

Wang, F, Stewart, J.A., Kasbek, C., Zhao, Y., Wright, W.E., Price, C.M.# (2012) Human CST has independent functions during telomere duplex replication and C-strand fill-in. Cell Reports. 2:1096-1103 doi: 10.1016/j.celrep.2012.10.007

Stewart, J.A.*, Wang, F.*, Chaiken, M.F., Kasbek, C., Chastain, P.D., Wright, W.E., Price, C.M.# (2012) Human CST promotes telomere duplex replication and general replication restart after fork stalling. EMBO Journal. 31:3537-3549 doi: 10.1038/emboj.2012.215

Price, C.M.#, Boltz, K.A., Chaiken, M.F., Stewart, J.A., Beilstein, M.A., Shippen, D.E.# (2010) Evolution of CST function in telomere maintenance. Cell Cycle. 9:3157-3165 doi: 10.4161/cc.916.12547

Balakrishnan, L.*, Stewart, J.A.*, Polaczek P., Campbell J.L., Bambara, R.A.# (2010) Acetylation of Dna2 and FEN1 by p300 promotes DNA stability by creating long flap intermediates. Journal of Biological Chemistry, 285:4398-4404 doi: 10.1074/jbc.M109.086397

Stewart, J. A., Campbell, J.L., Bambara, R.A.# (2010) Dna2 is a structural specific nuclease, with affinity for 5' flap intermediates. Nucleic Acids Research, 38:920-930 doi: 10.1093/nar/gkp1055

Stewart, J. A., Campbell, J.L., Bambara, R.A.# (2009) Significance of the dissociation of Dna2 by flap Endonuclease 1 to Okazaki fragment processing in Saccharomyces cerevisiae. Journal of Biological Chemistry, 284: 8283-8291 doi: 10.1074/jbc.M809189200

Stewart, J.A., Miller, A.S., Campbell, J.L., Bambara, R.A.# (2008) Dynamic removal of replication protein A by Dna2 facilitates primer cleavage during Okazaki fragment processing in Saccharomyces cerevisiae. Journal of Biological Chemistry, 283:31356-31365 doi: 10.1074/jbc.M805965200

Stewart, J.A., Campbell, J.L., Bambara, R.A.# (2006) Flap endonuclease disengages Dna2 nuclease/helicase from Okazaki fragment flaps. Journal of Biological Chemistry. 281:38565-38572 doi: 10.1074/jbc.M606884200

Hevel, J.M., Stewart, J.A., Gross, K.L., Ayling, J.E.# (2006) Can the DCoHalpha isozyme compensate in patients with 4a-hydroxy-tetrahydrobiopterin dehydratase/DCoH deficiency? Molecular Genetics and Metabolism. 88:38-46. doi: 10.1016/j.ymgme.2005.11.014
Invited Review Articles and Book Chapters

Schuck P.L.^, Ackerson, S.M.^, Stewart, J.A.# (2023) Telomere biology. In R.A. Bradshaw, G.W. Hart, P.H. Stahl (Eds.) Encyclopedia of Cell Biology (2nd ed.) Elsevier Inc. 1:523-531 doi: 10.1016/B978-0-12-821618-7.00099-7

Ackerson, S.A.^, Schuck, P.L.^, Romney, C., Stewart, J.A. # (2021) To join or not to join: Decisions along the along the path to double-strand break repair versus chromosome end protection. Frontiers in Cell and Development Biology. 9:708763 doi: 10.3389/fcell.2021.708763

Par, S., Vaides, S., VanderVere-Carozza, P.S., Pawelczak, K.S., Stewart, J.A., Turchi, J.J. # (2021) OB-folds and genome maintenance: Targeting protein-DNA interactions for cancer therapy. Cancers. 13:3346-358 doi: 10.3390/cancers13133346

Schuck, P.L.^, Stewart, J.A.# (2019) FISHing for DNA damage on metaphase chromosomes. Methods in Molecular Biology. 1999:335-347 doi: 10.1007/978-1-4939-9500-4_24

Stewart, J.A.#, Wang Y., Ackerson, S.M.^, Schuck, P.L.^ (2018) Emerging roles of CST in maintaining genome stability and human disease. Frontiers in Biosciences. 1:1564-1586 doi: 10.2741/4661