Department of Molecular and Cellular Medicine, Member of the GSBS Faculty
Room 440 Reynolds Medical Building / Lab Room 455
Education and Post-Graduate Training
Dr. Kapler received his B.S. in Biology from the University of Connecticut in 1979 and his Ph.D. in Genetics from Harvard University in 1989, working with Stephen Beverley. He did his postdoctoral research with the 2009 Nobel Laureate in Medicine, Elizabeth Blackburn, at the University of California, San Francisco. He joined the faculty at Texas A&M in 1994. Dr. Kapler is also a Member of Biochemistry and Biophysics and served as the chair of the Interdisciplinary Program in Genetics. In 2007 he was named Associate Department Head. In 2010 he was named Interim Departmental Chair. He has taught courses in medical genetics, yeast genetics, the cell cycle and chromosome biology.
Current research in chromosome biology is focused on understanding how trans-acting factors regulate replication initiation and the DNA damage checkpoint response. Work with the model eukaryote, Tetrahymena thermophila, has established new paradigms in the field. For example, recognition of the ribosomal DNA (rDNA) replication origin by the evolutionarily conserved, multi-subunit origin recognition complex (ORC) is mediated by a novel integral RNA subunit. This molecule, designated 26T RNA, corresponds to the 3’ end of 26S ribosomal RNA, and undergoes Watson-Crick base pairing with regulatory sequences at the rDNA origin. While 26T RNA is a component of all ORC complexes, it does not target ORC to other replication origins. This distinction may form the basis for the selective amplification of rDNA minichromosomes during development. Another rDNA binding factor, TIF1, prevents early firing of this replication origin. TIF1 mutants fail to trigger the DNA damage checkpoint response and exhibit gross genome instability, suggesting a more global role in chromosome homeostasis.
- Lee PH, Meng X, Kapler GM. (2015) Developmental Regulation of the Tetrahymena thermophila Origin Recognition Complex. PLoS Genet. 11(1):e1004875. doi: 10.1371/journal.pgen.1004875. eCollection 2015 Jan. PMID: 25569357 http://www.ncbi.nlm.nih.gov/pubmed/25569357
- Gao S, Xiong J, Zhang C, Berquist BR, Yang R, Zhao M, Molascon AJ, Kwiatkowski SY, Yuan D, Qin Z, Wen J, Kapler GM, Andrews PC, Miao W, Liu Y. (2013) Impaired replication elongation in Tetrahymena mutants deficient in histone H3 Lys 27 monomethylation. Genes Dev. 27(15):1662-79. doi: 10.1101/gad.218966.113. Epub 2013 Jul 24. PMID: 23884606 http://www.ncbi.nlm.nih.gov/pubmed/23884606
- Donti, T.R., Datta, S., Sandoval, P.Y., and Kapler, G.M. (2009) Differential targeting of Tetrahymena ORC to ribosomal DNA and non-rDNA replication origins. EMBO J. 28(3): 223-233. PMID: 19153611 http://www.ncbi.nlm.nih.gov/pubmed/19153611
- Mohammad, M.M., Smith, A.G., Donti, T.R., and Kapler, G.M. (2007) Tetrahymena ORC contains a ribosomal RNA fragment that participates in rDNA origin recognition. EMBO Journal. 26,5048-5060. PMID: 18007594 http://www.ncbi.nlm.nih.gov/pubmed/18007594
- Yakisich, J.S., and Kapler, G.M. (2006) Deletion of the Tetrahymena thermophila rDNA replication fork barrier region disrupts macronuclear rDNA excision and creates a fragile site in the micronuclear genome. Nucleic Acids Res. 34, 620-634. PMID: 16449202 http://www.ncbi.nlm.nih.gov/pubmed/16449202
- Yakisich, J.S., Sandoval, P.Y., Morrison, T.L., and Kapler, G.M. (2006) TIF1 activates the intra-S phase checkpoint response in the diploid micronucleus and amitotic polyploid macronucleus of Tetrahymena. Molecular Biology of the Cell. 17,5185-5197. PMID: 17005912 http://www.ncbi.nlm.nih.gov/pubmed/17005912
- Morrison, T.L., Yakisich, J.S., Cassidy-Hanley, D., and Kapler, G.M. (2005) TIF1 represses rDNA replication initiation, but promotes normal S phase progression and chromosome transmission in Tetrahymena. Mol. Biol. Cell. 16, 2624-2635. PMID: 15772155 http://www.ncbi.nlm.nih.gov/pubmed/15772155
- Smith, J.J., Yakisich, J.S., Kapler, G.M., Cole, E.S., and Romero, D.P. (2004) A beta-tubulin mutation selectively uncouples nuclear division and cytokinesis in Tetrahymena thermophila. Eukaryot Cell. 3,1217-1226. PMID: 15470250 http://www.ncbi.nlm.nih.gov/pubmed/15470250
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