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 Park, P. U.
Right arrow Articles by Guarente, L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Park, P. U.
Right arrow Articles by Guarente, L.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, May 1999, p. 3848-3856, Vol. 19, No. 5
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Effects of Mutations in DNA Repair Genes on Formation of Ribosomal DNA Circles and Life Span in Saccharomyces cerevisiae

Peter U. Park, Pierre-Antoine Defossez, and Leonard Guarente*

Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139

Received 16 December 1998/Returned for modification 29 January 1999/Accepted 24 February 1999

A cause of aging in Saccharomyces cerevisiae is the accumulation of extrachromosomal ribosomal DNA circles (ERCs). Introduction of an ERC into young mother cells shortens life span and accelerates the onset of age-associated sterility. It is important to understand the process by which ERCs are generated. Here, we demonstrate that homologous recombination is necessary for ERC formation. rad52 mutant cells, defective in DNA repair through homologous recombination, do not accumulate ERCs with age, and mutations in other genes of the RAD52 class have varying effects on ERC formation. rad52 mutation leads to a progressive delocalization of Sir3p from telomeres to other nuclear sites with age and, surprisingly, shortens life span. We speculate that spontaneous DNA damage, perhaps double-strand breaks, causes lethality in mutants of the RAD52 class and may be an initial step of aging in wild-type cells.

* Corresponding author. Mailing address: Department of Biology, Room 68-280, 77 Massachusetts Ave., Cambridge, MA 02139. Phone: (617) 253-0809. Fax: (617) 253-8699. E-mail: leng{at}mit.edu.

Molecular and Cellular Biology, May 1999, p. 3848-3856, Vol. 19, No. 5
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Richard, G.-F., Kerrest, A., Dujon, B. (2008). Comparative Genomics and Molecular Dynamics of DNA Repeats in Eukaryotes. Microbiol. Mol. Biol. Rev. 72: 686-727 [Abstract] [Full Text]  
  • Laun, P., Bruschi, C. V., Richard Dickinson, J., Rinnerthaler, M., Heeren, G., Schwimbersky, R., Rid, R., Breitenbach, M. (2007). Yeast mother cell-specific ageing, genetic (in)stability, and the somatic mutation theory of ageing. Nucleic Acids Res 0: gkm919v2-gkm919 [Abstract] [Full Text]  
  • Grenetier, S., Bouchoux, C., Goguel, V. (2006). CTD kinase I is required for the integrity of the rDNA tandem array. Nucleic Acids Res 34: 4996-5006 [Abstract] [Full Text]  
  • Coulon, S., Noguchi, E., Noguchi, C., Du, L.-L., Nakamura, T. M., Russell, P. (2006). Rad22Rad52-dependent Repair of Ribosomal DNA Repeats Cleaved by Slx1-Slx4 Endonuclease. Mol. Biol. Cell 17: 2081-2090 [Abstract] [Full Text]  
  • Azam, M., Lee, J. Y., Abraham, V., Chanoux, R., Schoenly, K. A., Johnson, F. B. (2006). Evidence that the S.cerevisiae Sgs1 protein facilitates recombinational repair of telomeres during senescence. Nucleic Acids Res 34: 506-516 [Abstract] [Full Text]  
  • Calzada, A., Hodgson, B., Kanemaki, M., Bueno, A., Labib, K. (2005). Molecular anatomy and regulation of a stable replisome at a paused eukaryotic DNA replication fork. Genes Dev. 19: 1905-1919 [Abstract] [Full Text]  
  • Michel, A. H., Kornmann, B., Dubrana, K., Shore, D. (2005). Spontaneous rDNA copy number variation modulates Sir2 levels and epigenetic gene silencing. Genes Dev. 19: 1199-1210 [Abstract] [Full Text]  
  • Kaeberlein, M., McDonagh, T., Heltweg, B., Hixon, J., Westman, E. A., Caldwell, S. D., Napper, A., Curtis, R., DiStefano, P. S., Fields, S., Bedalov, A., Kennedy, B. K. (2005). Substrate-specific Activation of Sirtuins by Resveratrol. J. Biol. Chem. 280: 17038-17045 [Abstract] [Full Text]  
  • Kaeberlein, M., Andalis, A. A., Liszt, G. B., Fink, G. R., Guarente, L. (2004). Saccharomyces cerevisiae SSD1-V Confers Longevity by a Sir2p-Independent Mechanism. Genetics 166: 1661-1672 [Abstract] [Full Text]  
  • Torres, J. Z., Bessler, J. B., Zakian, V. A. (2004). Local chromatin structure at the ribosomal DNA causes replication fork pausing and genome instability in the absence of the S. cerevisiae DNA helicase Rrm3p. Genes Dev. 18: 498-503 [Abstract] [Full Text]  
  • Borghouts, C., Benguria, A., Wawryn, J., Jazwinski, S. M. (2004). Rtg2 Protein Links Metabolism and Genome Stability in Yeast Longevity. Genetics 166: 765-777 [Abstract] [Full Text]  
  • Lin, S.-J., Ford, E., Haigis, M., Liszt, G., Guarente, L. (2004). Calorie restriction extends yeast life span by lowering the level of NADH. Genes Dev. 18: 12-16 [Abstract] [Full Text]  
  • Coulon, S., Gaillard, P.-H. L., Chahwan, C., McDonald, W. H., Yates, J. R. III, Russell, P. (2004). Slx1-Slx4 Are Subunits of a Structure-specific Endonuclease That Maintains Ribosomal DNA in Fission Yeast. Mol. Biol. Cell 15: 71-80 [Abstract] [Full Text]  
  • Falcon, A. A., Aris, J. P. (2003). Plasmid Accumulation Reduces Life Span in Saccharomyces cerevisiae. J. Biol. Chem. 278: 41607-41617 [Abstract] [Full Text]  
  • Bitterman, K. J., Medvedik, O., Sinclair, D. A. (2003). Longevity Regulation in Saccharomyces cerevisiae: Linking Metabolism, Genome Stability, and Heterochromatin. Microbiol. Mol. Biol. Rev. 67: 376-399 [Abstract] [Full Text]  
  • Cohen, S., Yacobi, K., Segal, D. (2003). Extrachromosomal Circular DNA of Tandemly Repeated Genomic Sequences in Drosophila. Genome Res 13: 1133-1145 [Abstract] [Full Text]  
  • Ayyadevara, S., Ayyadevara, R., Vertino, A., Galecki, A., Thaden, J. J., Reis, R. J. S. (2003). Genetic Loci Modulating Fitness and Life Span in Caenorhabditis elegans: Categorical Trait Interval Mapping in CL2a x Bergerac-BO Recombinant-Inbred Worms. Genetics 163: 557-570 [Abstract] [Full Text]  
  • Kaeberlein, M., Andalis, A. A., Fink, G. R., Guarente, L. (2002). High Osmolarity Extends Life Span in Saccharomyces cerevisiae by a Mechanism Related to Calorie Restriction. Mol. Cell. Biol. 22: 8056-8066 [Abstract] [Full Text]  
  • Bitterman, K. J., Anderson, R. M., Cohen, H. Y., Latorre-Esteves, M., Sinclair, D. A. (2002). Inhibition of Silencing and Accelerated Aging by Nicotinamide, a Putative Negative Regulator of Yeast Sir2 and Human SIRT1. J. Biol. Chem. 277: 45099-45107 [Abstract] [Full Text]  
  • Ohya, T., Kawasaki, Y., Hiraga, S.-I., Kanbara, S., Nakajo, K., Nakashima, N., Suzuki, A., Sugino, A. (2002). The DNA Polymerase Domain of polepsilon Is Required for Rapid, Efficient, and Highly Accurate Chromosomal DNA Replication, Telomere Length Maintenance, and Normal Cell Senescence in Saccharomyces cerevisiae. J. Biol. Chem. 277: 28099-28108 [Abstract] [Full Text]  
  • Hoopes, L. L. M., Budd, M., Choe, W., Weitao, T., Campbell, J. L. (2002). Mutations in DNA Replication Genes Reduce Yeast Life Span. Mol. Cell. Biol. 22: 4136-4146 [Abstract] [Full Text]  
  • Anderson, R. M., Bitterman, K. J., Wood, J. G., Medvedik, O., Cohen, H., Lin, S. S., Manchester, J. K., Gordon, J. I., Sinclair, D. A. (2002). Manipulation of a Nuclear NAD+ Salvage Pathway Delays Aging without Altering Steady-state NAD+ Levels. J. Biol. Chem. 277: 18881-18890 [Abstract] [Full Text]  
  • Lewis, L. K., Karthikeyan, G., Westmoreland, J. W., Resnick, M. A. (2002). Differential Suppression of DNA Repair Deficiencies of Yeast rad50, mre11 and xrs2 Mutants by EXO1 and TLC1 (the RNA Component of Telomerase). Genetics 160: 49-62 [Abstract] [Full Text]  
  • Wai, H., Johzuka, K., Vu, L., Eliason, K., Kobayashi, T., Horiuchi, T., Nomura, M. (2001). Yeast RNA Polymerase I Enhancer Is Dispensable for Transcription of the Chromosomal rRNA Gene and Cell Growth, and Its Apparent Transcription Enhancement from Ectopic Promoters Requires Fob1 Protein. Mol. Cell. Biol. 21: 5541-5553 [Abstract] [Full Text]  
  • Cohen, S., Mechali, M. (2001). A novel cell-free system reveals a mechanism of circular DNA formation from tandem repeats. Nucleic Acids Res 29: 2542-2548 [Abstract] [Full Text]  
  • McVey, M., Kaeberlein, M., Tissenbaum, H. A., Guarente, L. (2001). The Short Life Span of Saccharomyces cerevisiae sgs1 and srs2 Mutants Is a Composite of Normal Aging Processes and Mitotic Arrest Due to Defective Recombination. Genetics 157: 1531-1542 [Abstract] [Full Text]  
  • Tomaska, L., Nosek, J., Makhov, A. M., Pastorakova, A., Griffith, J. D. (2000). Extragenomic double-stranded DNA circles in yeast with linear mitochondrial genomes: potential involvement in telomere maintenance. Nucleic Acids Res 28: 4479-4487 [Abstract] [Full Text]  
  • Kaeberlein, M., McVey, M., Guarente, L. (1999). The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms. Genes Dev. 13: 2570-2580 [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»