Effects of the human immunodeficiency virus type 1 Rev protein on reporter gene and host T-cell gene expression |
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Authors: | VC Bond MB Huang B Person R Hairston XY Ye M Saltarelli |
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Affiliation: | Department of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA. |
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Abstract: | The mechanism of DNA mismatch repair has been modeled upon biochemical studies of the E. coli DNA adenine methylation-instructed pathway where the initial recognition of mismatched nucleotides is performed by the MutS protein. MutS homologs (MSH) have been identified based on a highly conserved region containing a Walker-A adenine nucleotide binding motif. Here we show that adenine nucleotide binding and hydrolysis by the human mismatch recognition complex hMSH2-hMSH6 functions as a novel molecular switch. The hMSH2-hMSH6 complex is ON (binds mismatched nucleotides) in the ADP-bound form and OFF in the ATP-bound form. These results suggest a new model for the function of MutS proteins during mismatch repair in which the switch determines the timing of downstream events. |
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