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.

Li X, Hejna J, Moses RE.  The yeast Snm1 protein is a DNA 5’ –exonuclease.  DNA Repair 4:163-70 (2005).

Hussain S, Wilson JB, Medhurst AL, Hejna J, Witt E, Ananth S, Davies A, Masson JY, Moses R, West SC, de Winter JP, Ashworth A, Jones NJ, Mathew CG.  Direct interaction of FANCD2 with BRCA2 inDNA damage response pathways.  Hum Mol Genet 13(12):1241-8 (2004)

Bruun D, Folias A, Akkari Y, Cox Y, Olson S, Moses R.  siRNA depletion of BRCA1, but not BRCA2, causes increased genome instability in Fanconi anemia cells.  DNA Repair 2(9):1007-13 (2003)

Li X, Moses RE.  The beta-lactamase motif in Snm1 is required for repair of DNA double-strand breaks caused by interstrand crosslinks in S. cerevisiae.  DNA Repair 2(1):121-9 (2003)

Folias A, Matkovic M, Bruun D, Reid S, Hejna J, Grompe M, D’Andrea A, Moses R.  BRCA1 interacts directly with the Fanconi anemia protein FANCA.  Hum Mol Genet 11(21):2591-7(2002)

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