Raymond Monnat

Professor of Genome Sciences and of Pathology

phone: (206) 616-7392, (206) 543-6585
Health Sciences K-072C, Box 357705
monnat [ a t ] u.washington.edu
website

Research:

Our research focuses on molecular mechanisms that insure the faithful transmission of genetic information in human somatic cells, and on the generation of novel genome engineering reagents for biology & medicine.

Genetic stability mechanisms: We work on a small human gene family, the RecQ helicases, that play key roles in nucleic acid metabolism and genome stability assurance. Loss of function of three of these proteins, WRN, BLM and RECQ4, are associated with the heritable genetic instability/cancer predisposition diseases Werner, Bloom and Rothmund-Thomson syndromes. Loss of expression of several of these proteins may also be an important determinant of the response of common adult cancers to chemotherapy. Our research is focused on in vivo functions and functional redundancy between different RecQ proteins, and the role of RecQ variation and loss in determining human disease risk and the response to therapy.

Genome engineering: Homing endonucleases are highly site-specific endonucleases that catalyze the lateral transfer of parasitic DNA elements in all Kingdoms of life. We have characterized structures and target site specificities of members of two major families of these proteins, and are engineering novel variants with altered target site specificites. These new gene-specific reagents are being used for genome engineering, and have potential for disease therapy and prevention.

More information? More details on the above projects and lots more can be found on our lab website - follow the link from this page. Representative recent publications are listed below.

Selected Publications:

McConnell-Smith, A., Pellenz, S., Davis, L.W., Maizels, N., Monnat, R.J., Jr. and Stoddard, B.L. (2009) Generation of a nicking enzyme that stimulates site-specific targeted gene correction from the I-AniI LAGLIDADG homing endonuclease. Proc Natl Acad Sci USA 106: 5099-5104.
PMID: 19276110/PMCID: PMC2664052.

Li, H. Pellenz, S., Ulge, U. Stoddard, B.L. and Monnat, R.J., Jr. (2009) Generation of single-chain LAGLIDADG homing endonucleases from native homodimeric precursor proteins. Nucleic Acids Res. 37:1650-1662. PMID:19153140/PMCID: PMC2655683.

Sidorova, J.M., Li, N., Schwartz, D.C., Folch, A. and Monnat, R.J., Jr. (2009) Microfluidic-assisted analysis of replicating DNA molecules. Nature Protocols 4:849-861. PMID: 19444242

Rey, L., Sidorova, J.M., Puget, N., Boudsocq, F., Biard, D.S.F., Monnat, R.J., Jr., Cazaux, C. and Hoffman, J-S. (2009) Human DNA polymerase eta is required for common fragile site stability during unperturbed DNA replication Molec Cell Biol 29:3344-3350. PMID: 19380493.