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Research Interests
The main research interest of the laboratory is in the control, distribution and resolution of meiotic recombination in the yeast Saccharomyces cerevisiae and how the environment impacts on these decisions. Although much is known about where and how recombination events are initiated very little is known about some of the upstream and the down stream events. For example how homologues find each other is unknown. Once a recombination event is initiated how the bias favouring recombination with the homologue over the sister i.e. "partner choice" is established is not fully understood. Despite years of analysis it is also still unclear how the extent of heteroduplex formation is controlled. Finally, what controls when and how a recombination is resolved as a reciprocal crossover or not is unknown. Work from our group and that of others has shown that mismatch repair proteins play important roles in all of these processes from the simple repair of mismatches contained in heteroduplex DNA (gene conversion), promoting crossover resolution and to the complete or partial prevention of recombination between diverged sequences (homeologous recombination). We have shown that this latter aspect is a component to the barrier preventing hybridisation of species. We have also been instrumental in showing a mismatch independent role in crossover resolution for the MutL homologues, MLH1 and MLH3 one of the repair exonucleases, EXO1. We have also recently shown that the yeast homologue of the Blooms Syndrome protein, SGS1, is important in unwinding interaction between diverged sequences.
Because recombination is essential for chromosome segregation we, and others have proposed that defects in recombination genes may be associated with infertility. In the past few years we have used state of the art resequencing technology to find mutations of a number recombination genes (including those described above) in infertile men. A number of mutations have been found and are the subject of ongoing studies.
Other ongoing work includes a project to “humanize” yeast. This involves expressing the human homologues of the mismatch repair and recombination genes in yeast and assessing their wild-type function. If we can reconstitute wild type function we will be able easily assay any novel human mutations identified. Finally plans are in place to use SNP detection arrays to map crossovers genome wide in various recombination mutants and in environmental conditions that we know to perturb crossing over.
Recent Publications
COTTON, V. E., E. R. HOFFMAN, M. F. F. ABDULLAH and R. H. BORTS, 2009 The devil is in the details: The importance of genetic and environmental factors for yeast meiosis. Protocals for Meiosis in press
BORTS, R. H., 2009 The new yeast is a mouse. PLoS Biol in press.
ALDRED, P. M., and R. H. BORTS, 2007 Humanizing mismatch repair in yeast: towards effective identification of hereditary non-polyposis colorectal cancer alleles. Biochem Soc Trans 35: 1525-1528.
BORTS, R. H., and D. KIRKPATRICK, 2006 The role of the genome in the initiation of meiotic recombination, pp. 208-224 in The Implicit Genome, edited by L. CAPORALE. Oxford University Press, New York.
BACHRATI, C. Z., R. H. BORTS and I. D. HICKSON, 2006 Mobile D-loops are a preferred substrate for the Bloom's syndrome helicase. Nucleic Acids Res 34: 2269-2279.
HOFFMANN, E. R., E. ERIKSSON, B. J. HERBERT and R. H. BORTS, 2005 MLH1 and MSH2 promote the symmetry of double-strand break repair events at the HIS4 hotspot in Saccharomyces cerevisiae. Genetics 169: 1291-1303.
STAHL, F. W., H. M. FOSS, L. S. YOUNG, R. H. BORTS, M. F. ABDULLAH et al., 2004 Does crossover interference count in Saccharomyces cerevisiae? Genetics 168: 35-48.
HOFFMANN, E. R., and R. H. BORTS, 2004 Meiotic recombination intermediates and mismatch repair proteins. Cytogenet Genome Res 107: 232-248.
ABDULLAH, M. F., E. R. HOFFMANN, V. E. COTTON and R. H. BORTS, 2004
A role for the MutL homologue MLH2 in controlling heteroduplex formation and in regulating between two different crossover pathways in budding yeast. Cytogenet Genome Res 107: 180-190.
LOUIS, E. J., and R. H. BORTS, 2003 Meiotic recombination: too much of a good thing? Curr Biol 13: R953-955.
HOFFMANN, E. R., P. V. SHCHERBAKOVA, T. A. KUNKEL and R. H. BORTS, 2003 MLH1 mutations differentially affect meiotic functions in Saccharomyces cerevisiae. Genetics 163: 515-526.
GREIG, D., M. TRAVISANO, E. J. LOUIS and R. H. BORTS, 2003 A role for the mismatch repair system during incipient speciation in Saccharomyces. J Evol Biol 16: 429-437.
GREIG, D., E. J. LOUIS, R. H. BORTS and M. TRAVISANO, 2002 Hybrid speciation in experimental populations of yeast. Science 298: 1773-1775.
ABDULLAH, M. F., and R. H. BORTS, 2001 Meiotic recombination frequencies are affected by nutritional states in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 98: 14524-14529.
KHAZANEHDARI, K. A., and R. H. BORTS, 2000 EXO1 and MSH4 differentially affect crossing-over and segregation. Chromosoma 109: 94-102.
BORTS, R. H., S. R. CHAMBERS and M. F. ABDULLAH, 2000 The many faces of mismatch repair in meiosis. Mutat Res 451: 129-150.
HUNTER, N., and R. H. BORTS, 1997 Mlh1 is unique among mismatch repair proteins in its ability to promote crossing-over during meiosis. Genes Dev 11: 1573-1582.
WATT, P. M., I. D. HICKSON, R. H. BORTS and E. J. LOUIS, 1996 SGS1, a homologue of the Bloom's and Werner's syndrome genes, is required for maintenance of genome stability in Saccharomyces cerevisiae. Genetics 144: 935-945.
WATT, P. M., E. J. LOUIS, R. H. BORTS and I. D. HICKSON, 1995 Sgs1: a eukaryotic homolog of E. coli RecQ that interacts with topoisomerase II in vivo and is required for faithful chromosome segregation. Cell 81: 253-260.
BORTS, R. H., W. Y. LEUNG, W. KRAMER, B. KRAMER and M. WILLIAMSON, 1990 Mismatch repair-induced meiotic recombination requires the pms1 gene product. Genetics 124: 573-584.
LICHTEN, M., R. H. BORTS and J. E. HABER, 1987 Meiotic gene conversion and crossing over between dispersed homologous sequences occurs frequently in Saccharomyces cerevisiae. Genetics 115: 233-246.
BORTS, R. H., and J. E. HABER, 1987 Meiotic recombination in yeast: alteration by multiple heterozygosities. Science 237: 1459-1465.
BORTS, R. H., M. LICHTEN, M. HEARN, L. S. DAVIDOW and J. E. HABER, 1984 Physical monitoring of meiotic recombination in Saccharomyces cerevisiae. Cold Spring Harb Symp Quant Biol 49: 67-76.
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Prof R. Borts
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