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Molecular and Cellular Biology, August 2001, p. 5459-5470, Vol. 21, No. 16
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.16.5459-5470.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

High-Copy-Number Expression of Sub2p, a Member of the RNA Helicase Superfamily, Suppresses hpr1-Mediated Genomic Instability

Hua-Ying Fan,dagger Robert J. Merker, and Hannah L. Klein*

Department of Biochemistry and Kaplan Cancer Center, New York University Medical Center, New York, New York 10016

Received 31 January 2001/Returned for modification 14 February 2001/Accepted 21 May 2001

We report on a novel role for a pre-mRNA splicing component in genome stability. The Hpr1 protein, a component of an RNA polymerase II complex and required for transcription elongation, is also required for genome stability. Deletion of HPR1 results in a 1,000-fold increase in genome instability, detected as direct-repeat instability. This instability can be suppressed by the high-copy-number SUB2 gene, which is the Saccharomyces cerevisiae homologue of the human splicing factor hUAP56. Although SUB2 is essential, conditional alleles grown at the permissive temperature complement the essential function of SUB2 yet reveal nonessential phenotypes. These studies have uncovered a role for SUB2 in preventing genome instability. The genomic instability observed in sub2 mutants can be suppressed by high-copy-number HPR1. A deletion mutant of CDC73, a component of a PolII complex, is also unstable for direct repeats. This too is suppressed by high-copy-number SUB2. Thus, defects in both the transcriptional machinery and the pre-mRNA splicing machinery can be sources of genome instability. The ability of a pre-mRNA splicing factor to suppress the hyperrecombination phenotype of a defective PolII complex raises the possibility of integrating transcription, RNA processing, and genome stability or a second role for SUB2.

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

dagger Present address: Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114.

Molecular and Cellular Biology, August 2001, p. 5459-5470, Vol. 21, No. 16
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.16.5459-5470.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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