Stephen Kron, M.D., Ph.D.

Role of CDC28 cdk in Regulating DNA Replication, Mitosis and Development in Budding Yeast

Research Summary

The Kron laboratory is a highly collaborative group of cells biologists, geneticists, biochemists and chemists. Our major basic research efforts are directed at 1) dissecting cyclin depentent kinase structure and function in yeast, 2) defining roles for chromatin modifications in DNA damage response, and 3) developing novel mass spectrometry methods for phosphoproteomics and high throughput screening. We also pursue translational projects directed at 1) developing Bcr-Abl assays for diagnostics and antagonists for therapeutics and 2) discovering inhibitors of cellular response to DNA double strand breaks as an approach to radiosensitization.

Selected Papers

Kitazono AA, Garza DA and Kron SJ. (2003). "Mutations in the yeast cyclin-dependent kinase Cdc28 reveal a role in the spindle assembly checkpoint," Molecular Genetics and Genomics, 269:672-84.

Taneja N, Davis M, Choy JS, Beckett MA, Singh R, Kron SJ and Weichselbaum RR. (2004). Histone H2AX phosphorylation as a predictor of radiosensitivity and target for radiotherapy. J. Biol. Chem., 279:2273-2280.

Wysocki R and Kron SJ. (2004). Yeast cell death during damage arrest is independent of caspase or reactive oxygen species. J Cell Biol 166: 311-6.

Downs JA, Allard S, Jobin-Robitaille O, Javaheri A, Bouchard N, Kron SJ, Jackson SP and Cote J. (2004). Binding of chromatin-modifying activities to phosphorylated histone H2A at DNA damage sites. Mol Cell 16: 979-90.

Brueggemeier SB, Wu D, Kron SJ and Palecek SP. (2004). Protein-acrylamide copolymer hydrogels for array-based detection of tyrosine linase activity from cell lysates. Biomacromolecules 6:2765-75

Parker LL, Schilling AB, Kron SJ and Kent SB. (2005). Optimizing thiophosphorylation in the presence of competing phosphorylation with MALDI-TOF-MS detection J Proteome Res. 4: 1863-66.

Wysocki R, Javaheri A, Allard S, Sha F, Cote J and Kron SJ. (2005). Role of DOt1-dependent histone H3 methylation in G1 and S phase DNA damage checkpoint functions of Rad9. Mol Cell Biol 25: 8430-43.

Parker LL, Schilling AB, Kron SJ and Kent SBH. (2005). "Optimizing thiophosphorylation in the presence of competing phosphorylation with MALDI-TOF-MS detection," J. Proteome Res., 4:1863-66.

Wu D, Nair-Gill E, Sher DA, Campbell JM, Parker LL, Stock W, Kron SJ. (2005). "Assaying Bcr-Abl kinase activity and inhibition in whole cell extracts by phosphorylation of substrates immobilized on agarose beads," Anal. Biochem., 347:67-76.

Kao J, Milano MT, Javaheri A, Garofalo MC, Chmura SJ, Weichselbaum RR and Kron SJ. (2006). "g-H2AX as a therapeutic target for improving the efficacy of radiation therapy," Curr. Cancer Drug Targets, 6:89-105.

Javaheri A, Wysocki R, Jobin-Robitaille O, Altaf M, Cote J and Kron SJ. (2006). "Yeast G1 DNA damage checkpoint regulation by H2A phosphorylation is independent of chromatin remodeling," Proc. Natl. Acad. Sci. U.S.A., 103:13771-6.

Parker LL, Brueggemeier SB, Rhee W-J, Wu D, Kent SB, Kron SJ and Palecek SP. (2006). "Photocleavable peptide hydrogel arrays for MALDI-TOF analysis of kinase activity," The Analyst, 131:1097-104.

Parker LL, Kurutz JW, Kent SB and Kron SJ. (2006). "Control of the yeast cell cycle with a photocleavable alpha-factor analog," Angewandte Chemie, 45:6322-5.

Wysocki R, Javaheri A, Sha F and Kron SJ. (2006). "CDK Pho85 targets CDK inhibitor Sic1 to relieve yeast G1 checkpoint arrest after DNA damage," Nature Struct. & Molec. Biol., 13:908-914.