Recombination between repeated sequences is an important genetic interaction in both maintaining and generating sequence diversity. A study of the regulation of recombination between repeated sequences in Saccharomyces cerevisiae is proposed. Regulation will be studied from a genetic and molecular approach. The proposed projects are: (1) A genetic study of repeat recombination in different mutant backgrounds. The types of recombination events that are increased in the hyper-recombination (hpr) mutants will be examined. The types of events that occur in different radiation sensitive (rad) mutants will also be characterized. (2) wild type alleles of hprl, hprll, and hpr12 will be cloned. The nucleotide and protein sequence will be determined. The clones will be used for studies of mRNA expression of the HPR genes. Null alleles and conditional alleles will be constructed in vitro and the in vivo phenotypes determined. Fusion constructions will be made to make fusion proteins for antibody preparation. The antibodies will be used to identify the protein product of the gene. (3) Overexpression of mutant forms of yeast topoisomerase II in yeast will be used to examine the role of topoisomerase II in recombination.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
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Genetics Study Section (GEN)
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New York University
Schools of Medicine
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Merker, Robert J; Klein, Hannah L (2002) Role of transcription in plasmid maintenance in the hpr1Delta mutant of Saccharomyces cerevisiae. Mol Cell Biol 22:8763-73
Merker, Robert J; Klein, Hannah L (2002) hpr1Delta affects ribosomal DNA recombination and cell life span in Saccharomyces cerevisiae. Mol Cell Biol 22:421-9
Klein, H L (2001) Spontaneous chromosome loss in Saccharomyces cerevisiae is suppressed by DNA damage checkpoint functions. Genetics 159:1501-9
Fan, H Y; Merker, R J; Klein, H L (2001) High-copy-number expression of Sub2p, a member of the RNA helicase superfamily, suppresses hpr1-mediated genomic instability. Mol Cell Biol 21:5459-70
Schneiter, R; Guerra, C E; Lampl, M et al. (2000) A novel cold-sensitive allele of the rate-limiting enzyme of fatty acid synthesis, acetyl coenzyme A carboxylase, affects the morphology of the yeast vacuole through acylation of Vac8p. Mol Cell Biol 20:2984-95
Chang, M; French-Cornay, D; Fan, H Y et al. (1999) A complex containing RNA polymerase II, Paf1p, Cdc73p, Hpr1p, and Ccr4p plays a role in protein kinase C signaling. Mol Cell Biol 19:1056-67
Schneiter, R; Guerra, C E; Lampl, M et al. (1999) The Saccharomyces cerevisiae hyperrecombination mutant hpr1Delta is synthetically lethal with two conditional alleles of the acetyl coenzyme A carboxylase gene and causes a defect in nuclear export of polyadenylated RNA. Mol Cell Biol 19:3415-22
Klein, H L (1997) RDH54, a RAD54 homologue in Saccharomyces cerevisiae, is required for mitotic diploid-specific recombination and repair and for meiosis. Genetics 147:1533-43
Fan, H Y; Cheng, K K; Klein, H L (1996) Mutations in the RNA polymerase II transcription machinery suppress the hyperrecombination mutant hpr1 delta of Saccharomyces cerevisiae. Genetics 142:749-59
Guerra, C E; Klein, H L (1995) Mapping of the ACC1/FAS3 gene to the right arm of chromosome XIV of Saccharomyces cerevisiae. Yeast 11:697-700

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