Research in the Lewis Group
The chromosomes within animal and plant cells are continually engaged in a cycle of DNA damage and repair. One common type of damage involves breakage of one or both of the long strands of the DNA double helix. This type of DNA damage is particularly prevalent after exposure of cells to agents such as X-rays or radon gas and is also induced by free radicals and by many chemicals used in cancer chemotherapy.
Restoration of the broken DNA double helix requires the coordinated activities of a large number of cellular proteins. The laboratory is applying modern techniques of molecular biology and biochemistry to identify and characterize genes involved in repair of strand breaks and other types of DNA damage. Several genes identified in this work have been found to affect other aspects of DNA metabolism, including cell cycle checkpoint responses and telomere stability. Furthermore, a subset of these genes encode proteins homologous to human proteins previously implicated in a number of human diseases, including cancer. Understanding these processes and the multiple pathways involved in DNA strand break repair are major goals of current research in the lab.
A second major effort in the lab involves the study of cellular aging. Most human cells stop producing telomerase, a DNA polymerase enzyme, early in development. Both in vivo and when grown in culture, the telomerase-deficient cells undergo progressive shortening at the ends of their chromosomes, at regions called telomeres. A new system developed in the lab allows modulated expression of telomerase inside cells. This expression system has been used to perform critical tests of current models for cell aging and cell death.
1. Jennifer Summers McKinney†, Sunaina Sethi†, Jennifer DeMars Tripp†, Thuy N. Nguyen†,
Brian A. Sanderson†, James W. Westmoreland, Michael A. Resnick and L. Kevin Lewis*.
2013. A multistep genomic screen identifies new genes required for repair of DNA
double-strand breaks in Saccharomyces cerevisiae. BMC Genomics 14:251-266.
2. Jennifer DeMars Tripp†, Jennifer L. Lilley‡, Whitney N. Wood‡ and L. Kevin Lewis*. 2013.
Enhancement of plasmid DNA transformation efficiencies in early stationary phase yeast cell
cultures. Yeast. 30:191-200.
3. Brian A. Sanderson†, Drew S. Sowersby†, Sergio Crosby, Marcus Goss, L. Kevin Lewis and
Gary W. Beall. 2013. Charge density and particle size effects on oligonucleotide and plasmid
DNA binding to nanosized hydrotalcite. Biointerphases. 8:8-18.
4. Sandra C. Becerra†, Hiranthi T. Thambugala†, Alison Russell Erickson†, Christopher K. Lee†
and L. Kevin Lewis*. 2012. Reversibility of replicative senescence in Saccharomyces
cerevisiae: effect of homologous recombination and cell cycle checkpoints. DNA Repair
11:35-45. (Published online November 9, 2011)
5. Christopher K. Lee†, Naoko Araki†, Drew S. Sowersby† and L. Kevin Lewis*. 2011. Factors
affecting chemical-based purification of DNA from Saccharomyces cerevisiae. Yeast
[Online] doi: 10.1002/yea.1918 (accessed Nov 15, 2011).
6. L. Kevin Lewis*, Michael H. Robson†, Yelena Vecherkina, Chang Ji and Gary W. Beall.
2010. Interference with spectrophotometric analysis of nucleic acids and proteins by leaching
of chemicals from plastic tubes. Biotechniques 48:297-302.
7. James W. Westmoreland, Jennifer A. Summers†, Cory L. Holland†, Michael A. Resnick and
L. Kevin Lewis*. 2010. Blunt-ended DNA double-strand breaks induced by endonucleases
PvuII and EcoRV are poor substrates for repair in Saccharomyces cerevisiae. DNA Repair
8. Gary W. Beall, Drew S. Sowersby‡, Rachel D. Roberts†, Michael H. Robson† and L. Kevin
Lewis*. 2009. Analysis of oligonucleotide DNA binding and sedimentation properties of
montmorillonite clay using ultraviolet light spectroscopy. Biomacromolecules 10:105-112.
9. Brian M. Wasko†, Cory L. Holland†, Michael A. Resnick and L. Kevin Lewis*. 2009.
Inhibition of DNA double-strand break repair by the Ku heterodimer in mrx mutants of
Saccharomyces cerevisiae. DNA Repair 8:162-169.