This Article Full Text Full Text (PDF) An erratum has been published Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Morishita, T. Articles by Shinagawa, H. Search for Related Content PubMed PubMed Citation Articles by Morishita, T. Articles by Shinagawa, H.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, May 2002, p. 3537-3548, Vol. 22, No. 10
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.10.3537-3548.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

The Schizosaccharomyces pombe rad60 Gene Is Essential for Repairing Double-Strand DNA Breaks Spontaneously Occurring during Replication and Induced by DNA-Damaging Agents

Takashi Morishita,¹ Yasuhiro Tsutsui,¹ Hiroshi Iwasaki,^1,2, and Hideo Shinagawa^1*

Department of Molecular Microbiology, Research Institute for Microbial Diseases, Osaka University,¹ PRESTO JST, Suita, Osaka 565-0871, Japan²

Received 13 December 2001/ Returned for modification 23 January 2002/ Accepted 22 February 2002

To identify novel genes involved in DNA double-strand break (DSB) repair, we previously isolated Schizosaccharomyces pombe mutants which are hypersensitive to methyl methanesulfonate (MMS) and synthetic lethals with rad2. This study characterizes one of these mutants, rad60-1. The gene that complements the MMS sensitivity of this mutant was cloned and designated rad60. rad60 encodes a protein with 406 amino acids which has the conserved ubiquitin-2 motif found in ubiquitin family proteins. rad60-1 is hypersensitive to UV and rays, epistatic to rhp51, and defective in the repair of DSBs caused by -irradiation. The rad60-1 mutant is also temperature sensitive for growth. At the restrictive temperature (37°C), rad60-1 cells grow for several divisions and then arrest with 2C DNA content; the arrested cells accumulate DSBs and have a diffuse and often aberrantly shaped nuclear chromosomal domain. The rad60-1 mutant is a synthetic lethal with rad18-X, and expression of wild-type rad60 from a multicopy plasmid partially suppresses the MMS sensitivity of rad18-X cells. rad18 encodes a conserved protein of the structural maintenance of chromosomes (SMC) family (A. R. Lehmann, M. Walicka, D. J. Griffiths, J. M. Murray, F. Z. Watts, S. McCready, and A. M. Carr, Mol. Cell. Biol. 15:7067-7080, 1995). These results suggest that S. pombe Rad60 is required to repair DSBs, which accumulate during replication, by recombination between sister chromatids. Rad60 may perform this function in concert with the SMC protein Rad18.

Present address: Science of Biological Supermolecular Systems, Graduate School of Integrated Science, Yokohama City University, Tsurumi-ku, Yokohama, Kanagawa, Japan.

This article has been cited by other articles:

• Akamatsu, Y., Murayama, Y., Yamada, T., Nakazaki, T., Tsutsui, Y., Ohta, K., Iwasaki, H. (2008). Molecular Characterization of the Role of the Schizosaccharomyces pombe nip1+/ctp1+ Gene in DNA Double-Strand Break Repair in Association with the Mre11-Rad50-Nbs1 Complex. Mol. Cell. Biol. 28: 3639-3651 [Abstract] [Full Text]  
• Lee, K. M., Nizza, S., Hayes, T., Bass, K. L., Irmisch, A., Murray, J. M., O'Connell, M. J. (2007). Brc1-Mediated Rescue of Smc5/6 Deficiency: Requirement for Multiple Nucleases and a Novel Rad18 Function. Genetics 175: 1585-1595 [Abstract] [Full Text]  
• Ampatzidou, E., Irmisch, A., O'Connell, M. J., Murray, J. M. (2006). Smc5/6 Is Required for Repair at Collapsed Replication Forks. Mol. Cell. Biol. 26: 9387-9401 [Abstract] [Full Text]  
• Raffa, G. D., Wohlschlegel, J., Yates, J. R. III, Boddy, M. N. (2006). SUMO-binding Motifs Mediate the Rad60-dependent Response to Replicative Stress and Self-association. J. Biol. Chem. 281: 27973-27981 [Abstract] [Full Text]  
• Kasama, T., Shigehisa, A., Hirata, A., Saito, T. T., Tougan, T., Okuzaki, D., Nojima, H. (2006). Spo5/Mug12, a Putative Meiosis-Specific RNA-Binding Protein, Is Essential for Meiotic Progression and Forms Mei2 Dot-Like Nuclear Foci.. Eukaryot Cell 5: 1301-1313 [Abstract] [Full Text]  
• Cost, G. J., Cozzarelli, N. R. (2006). Smc5p Promotes Faithful Chromosome Transmission and DNA Repair in Saccharomyces cerevisiae. Genetics 172: 2185-2200 [Abstract] [Full Text]  
• Miyabe, I., Morishita, T., Hishida, T., Yonei, S., Shinagawa, H. (2006). Rhp51-Dependent Recombination Intermediates That Do Not Generate Checkpoint Signal Are Accumulated in Schizosaccharomyces pombe rad60 and smc5/6 Mutants after Release from Replication Arrest. Mol. Cell. Biol. 26: 343-353 [Abstract] [Full Text]  
• Sheedy, D. M., Dimitrova, D., Rankin, J. K., Bass, K. L., Lee, K. M., Tapia-Alveal, C., Harvey, S. H., Murray, J. M., O'Connell, M. J. (2005). Brc1-Mediated DNA Repair and Damage Tolerance. Genetics 171: 457-468 [Abstract] [Full Text]  
• Morishita, T., Furukawa, F., Sakaguchi, C., Toda, T., Carr, A. M., Iwasaki, H., Shinagawa, H. (2005). Role of the Schizosaccharomyces pombe F-Box DNA Helicase in Processing Recombination Intermediates. Mol. Cell. Biol. 25: 8074-8083 [Abstract] [Full Text]  
• Diggle, C. P., Bentley, J., Knowles, M. A., Kiltie, A. E. (2005). Inhibition of double-strand break non-homologous end-joining by cisplatin adducts in human cell extracts. Nucleic Acids Res 33: 2531-2539 [Abstract] [Full Text]  
• Sergeant, J., Taylor, E., Palecek, J., Fousteri, M., Andrews, E. A., Sweeney, S., Shinagawa, H., Watts, F. Z., Lehmann, A. R. (2005). Composition and Architecture of the Schizosaccharomyces pombe Rad18 (Smc5-6) Complex. Mol. Cell. Biol. 25: 172-184 [Abstract] [Full Text]  
• Andrews, E. A., Palecek, J., Sergeant, J., Taylor, E., Lehmann, A. R., Watts, F. Z. (2005). Nse2, a Component of the Smc5-6 Complex, Is a SUMO Ligase Required for the Response to DNA Damage. Mol. Cell. Biol. 25: 185-196 [Abstract] [Full Text]  
• Morikawa, H., Morishita, T., Kawane, S., Iwasaki, H., Carr, A. M., Shinagawa, H. (2004). Rad62 Protein Functionally and Physically Associates with the Smc5/Smc6 Protein Complex and Is Required for Chromosome Integrity and Recombination Repair in Fission Yeast. Mol. Cell. Biol. 24: 9401-9413 [Abstract] [Full Text]  
• Pebernard, S., McDonald, W. H., Pavlova, Y., Yates, J. R. III, Boddy, M. N. (2004). Nse1, Nse2, and a Novel Subunit of the Smc5-Smc6 Complex, Nse3, Play a Crucial Role in Meiosis. Mol. Biol. Cell 15: 4866-4876 [Abstract] [Full Text]  
• Harvey, S. H., Sheedy, D. M., Cuddihy, A. R., O'Connell, M. J. (2004). Coordination of DNA Damage Responses via the Smc5/Smc6 Complex. Mol. Cell. Biol. 24: 662-674 [Abstract] [Full Text]  
• McDonald, W. H., Pavlova, Y., Yates, J. R. III, Boddy, M. N. (2003). Novel Essential DNA Repair Proteins Nse1 and Nse2 Are Subunits of the Fission Yeast Smc5-Smc6 Complex. J. Biol. Chem. 278: 45460-45467 [Abstract] [Full Text]  
• Durant, S., Karran, P. (2003). Vanillins--a novel family of DNA-PK inhibitors. Nucleic Acids Res 31: 5501-5512 [Abstract] [Full Text]  
• Ueno, M., Nakazaki, T., Akamatsu, Y., Watanabe, K., Tomita, K., Lindsay, H. D., Shinagawa, H., Iwasaki, H. (2003). Molecular Characterization of the Schizosaccharomyces pombe nbs1+ Gene Involved in DNA Repair and Telomere Maintenance. Mol. Cell. Biol. 23: 6553-6563 [Abstract] [Full Text]  
• Boddy, M. N., Shanahan, P., McDonald, W. H., Lopez-Girona, A., Noguchi, E., Yates III, J. R., Russell, P. (2003). Replication Checkpoint Kinase Cds1 Regulates Recombinational Repair Protein Rad60. Mol. Cell. Biol. 23: 5939-5946 [Abstract] [Full Text]  
• Garcia, V., Bruchet, H., Camescasse, D., Granier, F., Bouchez, D., Tissier, A. (2003). AtATM Is Essential for Meiosis and the Somatic Response to DNA Damage in Plants. Plant Cell 15: 119-132 [Abstract] [Full Text]