| Biochemistry
of homologous recombination 
Characterization
of recombinase function in vivo
Characterization
of DNA intermediates in meiotic recombination
Genetic dissection
of BRCA1 function
Intergenic suppression
of BRCA1 function
Characterization
of drugs that alter the efficiency of homologous recombination
The breast cancer susceptibility
gene BRCA encodes a huge protein that is proposed to function
in a number of mechanistically unrelated biological pathways.
We are interested in the role of BRCA1 in homologous recombination
reactions. We found that the function of BRCA1 in homologous recombination
can be bypassed by elevating expression levels of recombinase
Rad51. This and other findings indicate that BRCA1’s role
in recombination is mediated via its effect on the efficiency
with which Rad51 assembles at sites of DNA damage. Studies in
a variety of organisms also provide evidence that functions controlling
assembly of recombinase are not essential for the recombination
process itself so long as recombinase is expressed at sufficiently
high levels. These studies suggest that assembly factors serve
to regulate recombination by controlling when and where recombinase
filaments form. We hope to understand this regulation by characterizing
the properties of BRCA1-independent recombination. Currently we
are asking if BRCA1- independent recombination involves higher
than normal levels of interhomolog and/or ectopic recombination.
Clongenic survival
assay showing overexpression of RAD51 rescues. The x-ray
sensitivity of BRCA1-/- mutant cells but does not increase
the resistance of wild type cells.
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