This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Fan, H.-Y.
Right arrow Articles by Klein, H. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Fan, H.-Y.
Right arrow Articles by Klein, H. L.

 Previous Article  |  Next Article 

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.


This article has been cited by other articles:

  • Gomez-Gonzalez, B., Aguilera, A. (2009). R-loops do not accumulate in transcription-defective hpr1-101 mutants: implications for the functional role of THO/TREX. Nucleic Acids Res 0: gkp385v1-gkp385 [Abstract] [Full Text]  
  • Wang, X., Chinnam, M., Wang, J., Wang, Y., Zhang, X., Marcon, E., Moens, P., Goodrich, D. W. (2009). Thoc1 Deficiency Compromises Gene Expression Necessary for Normal Testis Development in the Mouse. Mol. Cell. Biol. 29: 2794-2803 [Abstract] [Full Text]  
  • Gottipati, P., Helleday, T. (2009). Transcription-associated recombination in eukaryotes: link between transcription, replication and recombination. Mutagenesis 24: 203-210 [Abstract] [Full Text]  
  • Gonzalez-Aguilera, C., Tous, C., Gomez-Gonzalez, B., Huertas, P., Luna, R., Aguilera, A. (2008). The THP1-SAC3-SUS1-CDC31 Complex Works in Transcription Elongation-mRNA Export Preventing RNA-mediated Genome Instability. Mol. Biol. Cell 19: 4310-4318 [Abstract] [Full Text]  
  • Li, X., Niu, T., Manley, J. L. (2007). The RNA binding protein RNPS1 alleviates ASF/SF2 depletion-induced genomic instability. RNA 13: 2108-2115 [Abstract] [Full Text]  
  • Huertas, P., Garcia-Rubio, M. L., Wellinger, R. E., Luna, R., Aguilera, A. (2006). An hpr1 Point Mutation That Impairs Transcription and mRNP Biogenesis without Increasing Recombination. Mol. Cell. Biol. 26: 7451-7465 [Abstract] [Full Text]  
  • Voynov, V., Verstrepen, K. J., Jansen, A., Runner, V. M., Buratowski, S., Fink, G. R. (2006). Genes with internal repeats require the THO complex for transcription. Proc. Natl. Acad. Sci. USA 103: 14423-14428 [Abstract] [Full Text]  
  • Li, X., Manley, J. L. (2006). Cotranscriptional processes and their influence on genome stability. Genes Dev. 20: 1838-1847 [Abstract] [Full Text]  
  • Jimeno, S., Luna, R., Garcia-Rubio, M., Aguilera, A. (2006). Tho1, a Novel hnRNP, and Sub2 Provide Alternative Pathways for mRNP Biogenesis in Yeast THO Mutants. Mol. Cell. Biol. 26: 4387-4398 [Abstract] [Full Text]  
  • Wang, X., Chang, Y., Li, Y., Zhang, X., Goodrich, D. W. (2006). Thoc1/Hpr1/p84 Is Essential for Early Embryonic Development in the Mouse.. Mol. Cell. Biol. 26: 4362-4367 [Abstract] [Full Text]  
  • Sims, R. J. III, Belotserkovskaya, R., Reinberg, D. (2004). Elongation by RNA polymerase II: the short and long of it. Genes Dev. 18: 2437-2468 [Abstract] [Full Text]  
  • Rondon, A. G., Jimeno, S., Garcia-Rubio, M., Aguilera, A. (2003). Molecular Evidence That the Eukaryotic THO/TREX Complex Is Required for Efficient Transcription Elongation. J. Biol. Chem. 278: 39037-39043 [Abstract] [Full Text]  
  • Gallardo, M., Luna, R., Erdjument-Bromage, H., Tempst, P., Aguilera, A. (2003). Nab2p and the Thp1p-Sac3p Complex Functionally Interact at the Interface between Transcription and mRNA Metabolism. J. Biol. Chem. 278: 24225-24232 [Abstract] [Full Text]  
  • Estruch, F., Cole, C. N. (2003). An Early Function during Transcription for the Yeast mRNA Export Factor Dbp5p/Rat8p Suggested by Its Genetic and Physical Interactions with Transcription Factor IIH Components. Mol. Biol. Cell 14: 1664-1676 [Abstract] [Full Text]  
  • Merker, R. J., Klein, H. L. (2002). Role of Transcription in Plasmid Maintenance in the hpr1{Delta} Mutant of Saccharomyces cerevisiae. Mol. Cell. Biol. 22: 8763-8773 [Abstract] [Full Text]  
  • Zenklusen, D., Vinciguerra, P., Wyss, J.-C., Stutz, F. (2002). Stable mRNP Formation and Export Require Cotranscriptional Recruitment of the mRNA Export Factors Yra1p and Sub2p by Hpr1p. Mol. Cell. Biol. 22: 8241-8253 [Abstract] [Full Text]  
  • Libri, D., Dower, K., Boulay, J., Thomsen, R., Rosbash, M., Jensen, T. H. (2002). Interactions between mRNA Export Commitment, 3'-End Quality Control, and Nuclear Degradation. Mol. Cell. Biol. 22: 8254-8266 [Abstract] [Full Text]  
  • Hammell, C. M., Gross, S., Zenklusen, D., Heath, C. V., Stutz, F., Moore, C., Cole, C. N. (2002). Coupling of Termination, 3' Processing, and mRNA Export. Mol. Cell. Biol. 22: 6441-6457 [Abstract] [Full Text]  
  • Gonzalez-Barrera, S., Prado, F., Verhage, R., Brouwer, J., Aguilera, A. (2002). Defective nucleotide excision repair in yeast hpr1 and tho2 mutants. Nucleic Acids Res 30: 2193-2201 [Abstract] [Full Text]  
  • Chavez, S., Garcia-Rubio, M., Prado, F., Aguilera, A. (2001). Hpr1 Is Preferentially Required for Transcription of Either Long or G+C-Rich DNA Sequences in Saccharomyces cerevisiae. Mol. Cell. Biol. 21: 7054-7064 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»