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Molecular and Cellular Biology, May 1999, p. 3415-3422, Vol. 19, No. 5
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

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

Roger Schneiter,1 Cesar E. Guerra,2,dagger Manfred Lampl,1 Gabriela Gogg,1 Sepp D. Kohlwein,1 and Hannah L. Klein2,*

Institut für Biochemie und Lebensmittelchemie, Technische Universität Graz, A-8010 Graz, Austria,1 and Department of Biochemistry, New York University Medical Center, New York, New York 100162

Received 20 August 1998/Returned for modification 26 October 1998/Accepted 12 February 1999

In a screen for mutants that display synthetic lethal interaction with hpr1Delta , a hyperrecombination mutant of Saccharomyces cerevisiae, we have isolated a novel cold-sensitive allele of the acetyl coenzyme A (CoA) carboxylase gene, acc1cs, encoding the rate-limiting enzyme of fatty acid synthesis. The synthetic lethal phenotype of the acc1cs hpr1Delta double mutant was only partially complemented by exogenous fatty acids. hpr1Delta was also synthetically lethal with a previously isolated, temperature-sensitive allele of ACC1, mtr7 (mRNA transport), indicating that the lethality of the acc1cs hpr1Delta double mutant was not allele specific. The basis for the interaction between conditional acc1 alleles and hpr1Delta was investigated in more detail. In the hpr1Delta mutant background, acetyl-CoA carboxylase enzyme activity was reduced about 15-fold and steady-state levels of biotinylated Acc1p and ACC1 mRNA were reduced 2-fold. The reduced Acc1p activity in hpr1Delta cells, however, did not result in an altered lipid or fatty acid composition of the mutant membranes but rendered cells hypersensitive to soraphen A, an inhibitor of Acc1p. Similar to mtr7, hpr1Delta and acc1cs mutant cells displayed a defect in nuclear export of polyadenylated RNA. Oversized transcripts were detected in hpr1Delta , and rRNA processing was disturbed, but pre-mRNA splicing appeared wild type. Surprisingly, the transport defect of hpr1Delta and acc1cs mutant cells was accompanied by an altered ring-shaped structure of the nucleolus. These observations suggest that the basis for the synthetic lethal interaction between hpr1Delta and acc1 may lie in a functional overlap of the two mutations in nuclear poly(A)+ RNA production and export that results in an altered structure of the nucleolus.

* Corresponding author. Mailing address: Department of Biochemistry, New York University Medical Center, 550 First Ave., New York, NY 10016. Phone: (212) 263-5778. Fax: (212) 263-8166. E-mail: kleinh01{at}mcrcr.med.nyu.edu.

dagger Present address: Department of Microbiology and Molecular Genetics, UMDNJ-New Jersey Medical School, Newark, NJ 07103.

Molecular and Cellular Biology, May 1999, p. 3415-3422, Vol. 19, No. 5
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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