R. Michael Liskay, PhD
Oregon Health & Science University
3181 SW Sam Jackson Park Road
Mail Code: L103
Portland, OR 97239
Office: 503 494-7703
Fax: 503 494-6886
We use yeast and mice to study DNA mismatch repair (MMR),which corrects mismatches and senses DNA damage. MMR gene mutations increase spontaneous mutation and predispose to hereditary and sporadic cancer. Using gene targeting strategies, we derive and study knockout mice for four MutL homologs, Mlh1, Pms1 or Pms2, and Mlh3. We have observed increased mutation and cancer risk in these animals although the severity varies between the different knockouts. In a related project, we have developed an assay using the site-specific recombinase Cre to stochastically inactivate tumor suppressor genes or activate oncogenes in the mouse. The system also uses a color marker (b-galactosidase) which is activated by the recombinase thus marking those celllineages experiencing inactivation (or activation) of the "loxp"-tagged tumor suppressors/oncogenes. One question being addressed is "What is the minimum number of gene alterations necessary to promote intestinal tumor formation and progression in the mouse?" Our studies in yeast are centered on a better understanding of mechanism and the gene products involved in DNA mismatch repair.
Erdeniz, N., Nguyen, M., Deschenes, S.M. and R.M. Liskay. Mutations affecting a putative MutLa endonuclease motif impact multiple mismatch repair functions. DNA Repair 6(10):1463-1470 (2007).
Tran, P.T., Fey, J.P., Erdeniz, N., Gellon, L., Boiteux, S. and R.M. Liskay. A mutation in EXO1 defines separable roles in DNA mismatch repair and post-replication repair. DNA Repair 6(11):1572-1583 (2007).
Liskay, R.M., Wheeler, L. J., Mathews, C.K. and N. Erdeniz. Involvement of deoxycytidylate deaminase in the response to S(n)1-type methylation DNA damage in budding yeast. Curr. Biol. 17(17):R755-757 (2007).
Miller, A.J., Dudley, S.D., Tsao, J.-L., Shibata, D. and R.M. Liskay. Tractable Cre-lox system for stochastic alteration of genes in mice. Nature Methods 5: 227-229 (2008).