of Work: To better understand the contribution by mismatch repair in genome stability, specifically as it relates to recombination between closely related sequences we investigated the E. coli methyl- directed repair proteins on recA-catalyzed strand transfer. This laboratory has continued studies in elucidating the role of MutS ATPase activity during homeologous recombination. In replication fidelity it has been proposed that MutL adds to the MutS-mismatch complex in an ATP- dependent fashion. Consequently,it is quite conceivable that the observed enhanced block by MutL in preventing recombination between diverged DNAs is by a similar mechanism. The approach used to explore MutS-dependent ATP hydrolysis was provided by two MutS mutants that maintain different single point mutations within the highly conserved nucleotide binding domain. These mutants were characterized for mismatch binding/repair and ATPase activity. In addition, these mutants were shown to uncouple the enhanced block by MutL in strand transfer between M13 and fd DNAs. Future work will focus on several topics of mismatch repair and strand transfer. I would like to address other mismatch repair components and their role when the density of mispaired bases is 1% or less. In addition, present studies are addressing dominant negative mutants of MutS related to nucleotide binding domain and the putative hth known to perturb heterodimer formation in higher cells. Current studies will continue to address E. coli MutS to see if is able to recognize Holliday junctions in vitro.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
Intramural Research (Z01)
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