Kristina <span>H.</span> Schmidt
Researcher

Kristina H. Schmidt

Overview

Discipline

    • Cancer Biology and Evolution Program

Education & Training

    • Leipzig University, Germany, MSc - Biology
    • University of Edinburgh, UK, PhD - Molecular Biology
    • University of California School of Medicine, Ludwig Institute for Cancer Research, Postdoctoral Fellow
Research

My research interests are in cancer genetics, DNA repair and recombination, DNA damage and mutagenesis, the DNA damage checkpoint response, and genome instability. Our current investigations focus on the REcQ-like DNA helicases Sgs1 (yeast) and BLM (human) to understand their role at the interface between DNA replication, repair and recombination and in the suppression of genome instability.  We are using model organisms (yeast, C.elegans) to identify genetic pathways required for the maintenance of genome stability and how these pathways interact with each other.  Besides genetic and biochemical approaches, we also use NMR to understand structure-function relationships and mass spectometry of complex mixtures to identify proteomic changes in mutant cells.  Significant effort in the lab is also dedicated to developing yeast models for functional and mutational characterization of human cancer genes, with a current focus on Bloom's helicase.

Publications

  • Shastri VM, Schmidt KH. Cellular defects caused by hypomorphic variants of the Bloom syndrome helicase gene BLM. Mol Genet Genomic Med. 2016 Jan;4(1):106-119. Pubmedid: 26788541. Pmcid: PMC4707026.
  • Syed S, Desler C, Rasmussen LJ, Schmidt KH. A Novel Rrm3 Function in Restricting DNA Replication via an Orc5-Binding Domain Is Genetically Separable from Rrm3 Function as an ATPase/Helicase in Facilitating Fork Progression. PLoS Genet. 2016 Dec;12(12):e1006451. Pubmedid: 27923055. Pmcid: PMC5140057.
  • Bastos de Oliveira FM, Kim D, Cussiol JR, Das J, Jeong MC, Doerfler L, Schmidt KH, Yu H, Smolka MB. Phosphoproteomics reveals distinct modes of Mec1/ATR signaling during DNA replication. Mol Cell. 2015 Mar;57(6):1124-1132. Pubmedid: 25752575. Pmcid: PMC4369404.
  • Kennedy JA, Syed S, Schmidt KH. Structural Motifs Critical for In Vivo Function and Stability of the RecQ-Mediated Genome Instability Protein Rmi1. PLoS One. 2015;10(12):e0145466. Pubmedid: 26717309. Pmcid: PMC4696737.
  • Zhang M, Xiang S, Joo HY, Wang L, Williams KA, Liu W, Hu C, Tong D, Haakenson J, Wang C, Zhang S, Pavlovicz RE, Jones A, Schmidt KH, Tang J, Dong H, Shan B, Fang B, Radhakrishnan R, Glazer PM, Matthias P, Koomen J, Seto E, Bepler G, Nicosia SV, Chen J, Li C, Gu L, Li GM, Bai W, Wang H, Zhang X. HDAC6 deacetylates and ubiquitinates MSH2 to maintain proper levels of MutSα. Mol Cell. 2014 Jul;55(1):31-46. Pubmedid: 24882211. Pmcid: PMC4188514.
  • Doerfler L, Schmidt KH. Exo1 phosphorylation status controls the hydroxyurea sensitivity of cells lacking the Pol32 subunit of DNA polymerases delta and zeta. DNA Repair (Amst). 2014 Dec;24:26-36. Pubmedid: 25457771. Pmcid: PMC4418189.
  • Kennedy JA, Daughdrill GW, Schmidt KH. A transient α-helical molecular recognition element in the disordered N-terminus of the Sgs1 helicase is critical for chromosome stability and binding of Top3/Rmi1. Nucleic Acids Res. 2013 Dec;41(22):10215-10227. Pubmedid: 24038467. Pmcid: PMC3905885.
  • Mirzaei H, Schmidt KH. Non-Bloom syndrome-associated partial and total loss-of-function variants of BLM helicase. Proc Natl Acad Sci U S A. 2012 Nov;109(47):19357-19362. Pubmedid: 23129629. Pmcid: PMC3511070.
  • Illsinger S, Janzen N, Lücke T, Bednarczyk J, Schmidt KH, Hoy L, Sander J, Das AM. Cyclosporine A: impact on mitochondrial function in endothelial cells. Clin Transplant. 2012 Jan;25(4):584-593. Pubmedid: 20633034.
  • Doerfler L, Harris L, Viebranz E, Schmidt KH. Differential genetic interactions between Sgs1, DNA-damage checkpoint components and DNA repair factors in the maintenance of chromosome stability. Genome Integr. 2011 Oct;2:8. Pubmedid: 22040455. Pmcid: PMC3231943.
  • Mirzaei H, Syed S, Kennedy J, Schmidt KH. Sgs1 truncations induce genome rearrangements but suppress detrimental effects of BLM overexpression in Saccharomyces cerevisiae. J Mol Biol. 2011 Jan;405(4):877-891. Pubmedid: 21111748. Pmcid: PMC3065180.
  • Schmidt KH, Viebranz EB, Harris LB, Mirzaei-Souderjani H, Syed S, Medicus R. Defects in DNA lesion bypass lead to spontaneous chromosomal rearrangements and increased cell death. Eukaryot Cell. 2010 Feb;9(2):315-324. Pubmedid: 20008080. Pmcid: PMC2823012.
  • Vijayakumar S, Chapados BR, Schmidt KH, Kolodner RD, Tainer JA, Tomkinson AE. The C-terminal domain of yeast PCNA is required for physical and functional interactions with Cdc9 DNA ligase. Nucleic Acids Res. 2007 Apr;35(5):1624-1637. Pubmedid: 17308348. Pmcid: PMC1865074.
  • Schmidt K, Wu J, Kolodner R. Control of translocations between highly diverged genes by Sgs1, the Saccharomyces cerevisiae homolog of the Bloom's syndrome protein. Mol Cell Biol. 2006 Jul;26(14):5406-5420. Pubmedid: 16809776. Pmcid: PMC1592713.
  • Schmidt KH, Kolodner RD. Requirement of Rrm3 helicase for repair of spontaneous DNA lesions in cells lacking Srs2 or Sgs1 helicase. Mol Cell Biol. 2004 Apr;24(8):3213-3226. Pubmedid: 15060145. Pmcid: PMC381612.
  • Rödel J, Woytas M, Groh A, Schmidt KH, Hartmann M, Lehmann M, Straube E. Production of basic fibroblast growth factor and interleukin 6 by human smooth muscle cells following infection with Chlamydia pneumoniae. Infect Immun. 2000 Jun;68(6):3635-3641. Pubmedid: 10816522. Pmcid: PMC97653.
  • Reichardt W, Schmidt KH, Amberg C, Gubbe K. Mapping of binding sites for human serum albumin and fibrinogen on the M3-protein. Molecular model and function in the pathogenic mechanism. Adv Exp Med Biol. 1997;418:577-579. Pubmedid: 9331717.
  • Bruchelt G, Niethammer D, Schmidt KH. Isotachophoresis of nucleic acid constituents. Ai Zheng. 1993 Aug;618(1-2):57-77. Pubmedid: 8227265.
  • Schmidt KH, Bayer W. Efficacy of vitamin E as a drug in inflammatory joint diseases. Adv Exp Med Biol. 1990 Dec;264:147-150. Pubmedid: 2244487.
  • Oberritter H, Glatthaar B, Moser U, Schmidt KH. Effect of functional stimulation on ascorbate content in phagocytes under physiological and pathological conditions. Int Arch Allergy Appl Immunol. 1986;81(1):46-50. Pubmedid: 3744577.
  • Wadström T, Schmidt KH, Kühnemund O, Havlícek J, Köhler W. Comparative studies on surface hydrophobicity of streptococcal strains of groups A, B, C, D and G. J Gen Microbiol. 1984 Mar;130(3):657-664. Pubmedid: 6726181.
  • Bruchelt G, Schmidt KH. Comparative studies on the oxidative processes during phagocytosis measured by luminol-dependent chemiluminescence. J Clin Chem Clin Biochem. 1984 Jan;22(1):1-13. Pubmedid: 6421985.
  • Schubert R, Jaroni H, Schoelmerich J, Schmidt KH. Studies on the mechanism of bile salt-induced liposomal membrane damage. Digestion. 1983;28(3):181-190. Pubmedid: 6365666.
  • Schmidt KH, Hagmaier V, Hornig DH, Vuilleumier JP, Rutishauser G. Urinary oxalate excretion after large intakes of ascorbic acid in man. Am J Clin Nutr. 1981 Mar;34(3):305-311. Pubmedid: 7211731.
  • Sauer MC, Schmidt KH, Hart EJ, Naleway CA, Jonah CD. LET dependence of transient yields in the pulse radiolysis of aqueous systems with deuterons and alpha particles. Radiat Res. 1977 Apr;70(1):91-106. Pubmedid: 850737.