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Claire Cupples, Professor

BSc (hons) University of Victoria
MSc University of Calgary
PhD York University

Phone: (778) 782-3771
Office: SCP P9300
Email: ccupples@sfu.ca
Research website - forthcoming

Research Interest

  • DNA, the keeper of genetic information in all organisms, is constantly modified by internal and external factors during the cell's lifetime. Many types of DNA modification cause mutations. Although mutations may be harmful to individual cells or organisms, mutation in populations is valuable because it leads to genetic variation and ultimately to evolution. There are even circumstances when it is useful to increase the number of mutations in a cell, for example in genes that code for antibodies. Maintaining the optimal balance between genetic stability and variability requires the cell to balance the frequency with which modifications to the DNA occur, and the efficiency with which the original sequence is restored by the various DNA repair pathways. My lab is interested in three aspects of DNA repair and mutagenesis:


    1. Competition and cooperation among multiple DNA repair systems, and the central role of one protein - MutL - in coordinating these interactions. This research is done with the bacterium Escherichia coli, using a combination of genetics (to modulate DNA repair and to monitor the resulting changes in mutation frequencies in vivo) and biochemistry (to study the mechanism of protein-protein and protein-DNA interactions during repair, in vitro).
    2. The interaction among transcription, DNA repair and chromatin in maintaining genetic and epigenetic information. Defects in the mammalian DNA repair protein, MBD4, are associated with cancer - mechanism unknown. MBD4 is bifunctional, one domain acting as a DNA repair enzyme to minimize mutations caused by deamination of 5-methylcytosine, and a second domain acting to repress transcription in promotors containing 5-methylcytosine. The protein also interacts with chromatin, another modulator of gene expression. We are interested in the interplay between the domains, and the role of chromatin in modulating activity of the whole protein.
    3. DNA repair and nuclear dimorphism. Tetrahymena thermophila, a single-celled, ciliate protozoan, has two structurally and functionally distinct nuclei. One of them controls the phenotype of the cell and its daughters, while the other acts as a germ line, a repository of genetic information for future sexual generations. We are exploring the role of DNA repair in the life style and evolution of the two nuclei.

  • Publications
  • Polosina, YY, Cupples CG. (2011) Mutagenesis Mechanisms, Encyclopaedia of Life Sciences, Wiley-Blackwell.
  • Polosina YY, Cupples CG. (2010) Wot the 'L-Does MutL do? Mutat Res. 705: 228-38.
  • Polosina YY, Cupples CG. (2010) MutL: conducting the cell's response to mismatched and misaligned DNA. Bioessays. 32(1):51-9.
  • Polosina YY, Cupples CG. (2009) Changes in the conformation of the Vsr endonuclease amino-terminal domain accompany DNA cleavage. J. Biochem. 146(4):523-6.
  • Heinze RJ, Giron-Monzon L, Solovyova A, Elliot SL, Geisler S, Cupples CG, Connolly BA, Friedhoff P. (2009) Physical and functional interactions between Escherichia coli MutL and the Vsr repair endonuclease. Nucleic Acids Res. 37(13):4453-63.
  • Cupples CG (2009) DNA Repair, Encyclopedia of Microbiology, pp 99-112, Elsevier.
  • Polosina YY, Mui J, Pitsikas P, Cupples CG. (2009)The Escherichia coli mismatch repair protein MutL recruits the Vsr and MutH endonucleases in response to DNA damage. J. Bacteriol. 191(12):4041-3.
  • Pitsikas P, Polosina YY, Cupples CG. (2009) Interaction between the mismatch repair and nucleotide excision repair pathways in the prevention of 5-azacytidine-induced CG-to-GC mutations in Escherichia coli. DNA Repair (Amst). 8(3):354-9.
  • Ali M, Kim H, Cleary S, Cupples C, Gallinger S, Bristow R. (2008) Characterization of mutant MUTYH proteins associated with familial colorectal cancer. Gastroenterology. 135(2):499-507.
  • Ishibashi T, So K, Cupples CG, Ausi� J. (2008) MBD4-mediated glycosylase activity on a chromatin template is enhanced by acetylation. Mol Cell Biol. 28(15):4734-44.