My lab studies DNA crosslink repair using two model systems.  Fanconi anemia is a recessive disease affecting multiple organ systems and results in severe anemia and an increased risk of leukemia.  Cells from the patients are hypersensitive to DNA crosslinkers.  The Moses group is part of a program project on Fanconi anemia and has participated in the positional cloning of one of the genes, from among at least twelve.  The role of the FA genes inrepair of DNA cross links is intriguing not just because of the association with disease, but because the FA cells are competent in all other types of DNA repair tested.  Our current work is focused on the role of chromatin remodeling in FA and potential defects in remodeling which might affect ICL repair. 

A second project investigates the function a mammalian gene responsible for crosslink repair, the hSNM1 gene.  We have isolated the protein encoded by the gene and it is a 5’-exonuclease which is required for intermediate processing in the repair of ICLs.

1.   Hemphill, A., Bruun, D., Thrun, L., Akkari, Y., Torimaru, Y., Hejna, K., Jakobs, P.M., Hejna, J., Jones, S., Olson, S.B., and Moses, R.E.  Mammalian SNM1 is Required for Genome Stability, Molecular Genetics and Metabolism 94:38-45 (2008).  EPub, Nov. 2007

2.   Newell, A.H., Hemphill, A., Akkari, Y., Hejna, J., Moses, R.E., and Olson, S.B., Loss of Homologous Recombination or Non-homologous End Joining Leads to Radial Formation Following DNA Interstrand Crosslink Damage, Cytogenetic and Genome Res., 121:174-80 (2008), E-pub Aug, 2008.

3.   Hejna, J., Holtorf, M., Hines, J., Mathewson, L, Hemphill, A., Al-Dhalimy, M., Olson, S.B., and Moses, R.E. Tip60 is Required for DNA Interstrand Crosslink Repair in the Fanconi anemia Pathway, J. Biol. Chemistry 283:  9844-51 (2008).  EPub Feb, 2008.

4.   Minko, I., Harbut, M., Kozekov, A., Jakobs, Petra.M., Olson, S.B., Moses, R.E., Harris, T., Rizzo, C. and Lloyd, R.S. DNA Polymerase Kappa Catalyzes Error-free Translesion Synthesis past Repair Intermediates of N2-N3-guanine Interstrand Crosslinks, J. Biol. Chemistry, 283: 17075-17082 (2008), E-pub 4/22/08.

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