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 gene family, the human RecQ helicases, that play key roles in nucleic acid metabolism and genetic 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. Our research is focused on in vivo functions of these proteins, on regulation and on functional redundancy between different members of the human RecQ helicase family.
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 families of these proteins, and have used results to engineer novel chimeric homing endonucleases 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 both projects can be found on our lab website - follow the link from this page. Representative recent publications are listed below.
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Publications:
Ashworth, J., Havranek, J.J., Duarte, C.M., Sussman, D., Monnat, R.J., Jr., Stoddard, B.L. and Baker, D. (2006) Computational redesign of endonuclease DNA binding and cleavage specificity. Nature 441:656-659.
Dhillon,K., Sirorova, J., Saintigny,Y., Poot,M., Gollahon,K., Rabinovitch, P.S. and Monnat, R.J.,Jr. (2007) Functional role of the Werner syndrome RecQ helicase in human fibroblasts. Aging Cell 6: 53-61.
Volna, P., Jarjour, J. Baxter, S., Roffler, S., Monnat, RJ Jr., Stoddard, B. and Scharenberg, A. (2007) Flow cytometric analysis of DNA binding and cleavage by cell surface-displayed homing endonucleases. Nucleic Acids Research 35: 2748-2758.
Berkovich, E., Monnat, RJ Jr. and Kastan, M. (2007) Roles of ATM and NBS1 in chromatin structure modulation and DNA double strand break repair. Nature Cell Biology 9: 683-690.
Kudlow, B., Kennedy, B.K., and Monnat, RJ Jr. (2007) Werner and Hutchinson-Gilford progeria syndromes: mechanistic basis of human progeroid diseases. Nature Reviews Molecular and Cellular Biology 8: 394-404.
additional publication listings available via PubMed |
Office Phone: (206) 616-7392