Genetics, Vol 119, 779-790, Copyright © 1988

INVESTIGATIONS

Genetic Control of Intrachromosomal Recombination in Saccharomyces cerevisiae. I. Isolation and Genetic Characterization of Hyper-Recombination Mutations

A. Aguilera and H. L. Klein
Department of Biochemistry, New York University, New York, New York 10016

Eight complementation groups have been defined for recessive mutations conferring an increased mitotic intrachromosomal recombination phenotype (hpr genes) in Saccharomyces cerevisiae. Some of the mutations preferentially increase intrachromosomal gene conversion (hpr4, hpr5 and hpr8) between repeated sequences, some increase loss of a marker between duplicated genes (hpr1 and hpr6), and some increase both types of events (hpr2, hpr3 and hpr7). New alleles of the CDC2 and CDC17 genes were recovered among these mutants. The mutants were also characterized for sensitivity to DNA damaging agents and for mutator activity. Among the more interesting mutants are hpr5, which shows a biased gene conversion in a leu2-112::URA3::leu2-k duplication; and hpr1, which has a much weaker effect on interchromosomal mitotic recombination than on intrachromosomal mitotic recombination. These analyses suggest that gene conversion and reciprocal exchange can be separated mutationally. Further studies are required to show whether different recombination pathways or different outcomes of the same recombination pathway are controlled by the genes identified in this study.

This article has been cited by other articles:

				E. Mito, J. V. Mokhnatkin, M. C. Steele, V. L. Buettner, S. S. Sommer, G. M. Manthey, and A. M. Bailis Mutagenic and Recombinagenic Responses to Defective DNA Polymerase {delta} Are Facilitated by the Rev1 Protein in pol3-t Mutants of Saccharomyces cerevisiae Genetics, August 1, 2008; 179(4): 1795 - 1806. [Abstract] [Full Text] [PDF]

				Y. Hu, S. Raynard, M. G. Sehorn, X. Lu, W. Bussen, L. Zheng, J. M. Stark, E. L. Barnes, P. Chi, P. Janscak, et al. RECQL5/Recql5 helicase regulates homologous recombination and suppresses tumor formation via disruption of Rad51 presynaptic filaments Genes & Dev., December 1, 2007; 21(23): 3073 - 3084. [Abstract] [Full Text] [PDF]

				L. S. Symington and W.-D. Heyer Some disassembly required: role of DNA translocases in the disruption of recombination intermediates and dead-end complexes Genes & Dev., September 15, 2006; 20(18): 2479 - 2486. [Full Text] [PDF]

				J. A. Cobb and L. Bjergbaek RecQ helicases: lessons from model organisms Nucleic Acids Res., September 10, 2006; 34(15): 4106 - 4114. [Abstract] [Full Text] [PDF]

				P. Chi, Y. Kwon, C. Seong, A. Epshtein, I. Lam, P. Sung, and H. L. Klein Yeast Recombination Factor Rdh54 Functionally Interacts with the Rad51 Recombinase and Catalyzes Rad51 Removal from DNA J. Biol. Chem., September 8, 2006; 281(36): 26268 - 26279. [Abstract] [Full Text] [PDF]

				X. Li and J. L. Manley Cotranscriptional processes and their influence on genome stability Genes & Dev., July 15, 2006; 20(14): 1838 - 1847. [Abstract] [Full Text] [PDF]

				R. E. Wellinger, F. Prado, and A. Aguilera Replication Fork Progression Is Impaired by Transcription in Hyperrecombinant Yeast Cells Lacking a Functional THO Complex Mol. Cell. Biol., April 15, 2006; 26(8): 3327 - 3334. [Abstract] [Full Text] [PDF]

				A. Kato and H. Inoue Growth Defect and Mutator Phenotypes of RecQ-Deficient Neurospora crassa Mutants Separately Result From Homologous Recombination and Nonhomologous End Joining During Repair of DNA Double-Strand Breaks Genetics, January 1, 2006; 172(1): 113 - 125. [Abstract] [Full Text] [PDF]

				K. Suzuki, A. Kato, Y. Sakuraba, and H. Inoue Srs2 and RecQ homologs cooperate in mei-3-mediated homologous recombination repair of Neurospora crassa Nucleic Acids Res., March 30, 2005; 33(6): 1848 - 1858. [Abstract] [Full Text] [PDF]

				Y. Zhou and T. S.-F. Wang A Coordinated Temporal Interplay of Nucleosome Reorganization Factor, Sister Chromatin Cohesion Factor, and DNA Polymerase {alpha} Facilitates DNA Replication Mol. Cell. Biol., November 1, 2004; 24(21): 9568 - 9579. [Abstract] [Full Text] [PDF]

				F. Cortes-Ledesma, F. Malagon, and A. Aguilera A Novel Yeast Mutation, rad52-L89F, Causes a Specific Defect in Rad51-Independent Recombination That Correlates With a Reduced Ability of Rad52-L89F to Interact With Rad59 Genetics, September 1, 2004; 168(1): 553 - 557. [Abstract] [Full Text] [PDF]

				L. Maloisel, J. Bhargava, and G. S. Roeder A Role for DNA Polymerase {delta} in Gene Conversion and Crossing Over During Meiosis in Saccharomyces cerevisiae Genetics, July 1, 2004; 167(3): 1133 - 1142. [Abstract] [Full Text] [PDF]

				C. Soustelle, L. Vernis, K. Freon, A. Reynaud-Angelin, R. Chanet, F. Fabre, and M. Heude A New Saccharomyces cerevisiae Strain with a Mutant Smt3-Deconjugating Ulp1 Protein Is Affected in DNA Replication and Requires Srs2 and Homologous Recombination for Its Viability Mol. Cell. Biol., June 15, 2004; 24(12): 5130 - 5143. [Abstract] [Full Text] [PDF]

				M. Smirnova, S. Van Komen, P. Sung, and H. L. Klein Effects of Tumor-associated Mutations on Rad54 Functions J. Biol. Chem., June 4, 2004; 279(23): 24081 - 24088. [Abstract] [Full Text] [PDF]

				L. Krejci, M. Macris, Y. Li, S. Van Komen, J. Villemain, T. Ellenberger, H. Klein, and P. Sung Role of ATP Hydrolysis in the Antirecombinase Function of Saccharomyces cerevisiae Srs2 Protein J. Biol. Chem., May 28, 2004; 279(22): 23193 - 23199. [Abstract] [Full Text] [PDF]

				T. J. Westmoreland, J. R. Marks, J. A. Olson Jr., E. M. Thompson, M. A. Resnick, and C. B. Bennett Cell Cycle Progression in G1 and S Phases Is CCR4 Dependent following Ionizing Radiation or Replication Stress in Saccharomyces cerevisiae Eukaryot. Cell, April 1, 2004; 3(2): 430 - 446. [Abstract] [Full Text] [PDF]

				S. Van Komen, M. S. Reddy, L. Krejci, H. Klein, and P. Sung ATPase and DNA Helicase Activities of the Saccharomyces cerevisiae Anti-recombinase Srs2 J. Biol. Chem., November 7, 2003; 278(45): 44331 - 44337. [Abstract] [Full Text] [PDF]

				P. J. A. Gutierrez and T. S.-F. Wang Genomic Instability Induced by Mutations in Saccharomyces cerevisiae POL1 Genetics, September 1, 2003; 165(1): 65 - 81. [Abstract] [Full Text] [PDF]

				A. Galli, T. Cervelli, and R. H. Schiestl Characterization of the Hyperrecombination Phenotype of the pol3-t Mutation of Saccharomyces cerevisiae Genetics, May 1, 2003; 164(1): 65 - 79. [Abstract] [Full Text] [PDF]

				M. J. Swanson, H. Qiu, L. Sumibcay, A. Krueger, S.-j. Kim, K. Natarajan, S. Yoon, and A. G. Hinnebusch A Multiplicity of Coactivators Is Required by Gcn4p at Individual Promoters In Vivo Mol. Cell. Biol., April 15, 2003; 23(8): 2800 - 2820. [Abstract] [Full Text] [PDF]

				R. J. Merker and H. L. Klein Role of Transcription in Plasmid Maintenance in the hpr1{Delta} Mutant of Saccharomyces cerevisiae Mol. Cell. Biol., December 15, 2002; 22(24): 8763 - 8773. [Abstract] [Full Text] [PDF]

				M. Maftahi, J. C. Hope, L. Delgado-Cruzata, C. S. Han, and G. A. Freyer The severe slow growth of {Delta}srs2{Delta}rqh1 in Schizosaccharomyces pombe is suppressed by loss of recombination and checkpoint genes Nucleic Acids Res., October 15, 2002; 30(21): 4781 - 4792. [Abstract] [Full Text] [PDF]

				H. W. Mankouri, T. J. Craig, and A. Morgan SGS1 is a multicopy suppressor of srs2: functional overlap between DNA helicases Nucleic Acids Res., March 1, 2002; 30(5): 1103 - 1113. [Abstract] [Full Text] [PDF]

				S. Broomfield and W. Xiao Suppression of genetic defects within the RAD6 pathway by srs2 is specific for error-free post-replication repair but not for damage-induced mutagenesis Nucleic Acids Res., February 1, 2002; 30(3): 732 - 739. [Abstract] [Full Text] [PDF]

				R. J. Merker and H. L. Klein hpr1{Delta} Affects Ribosomal DNA Recombination and Cell Life Span in Saccharomyces cerevisiae Mol. Cell. Biol., January 15, 2002; 22(2): 421 - 429. [Abstract] [Full Text] [PDF]

				H. D. Ulrich The srs2 suppressor of UV sensitivity acts specifically on the RAD5- and MMS2-dependent branch of the RAD6 pathway Nucleic Acids Res., September 1, 2001; 29(17): 3487 - 3494. [Abstract] [Full Text] [PDF]

				H.-Y. Fan, R. J. Merker, and H. L. Klein High-Copy-Number Expression of Sub2p, a Member of the RNA Helicase Superfamily, Suppresses hpr1-Mediated Genomic Instability Mol. Cell. Biol., August 15, 2001; 21(16): 5459 - 5470. [Abstract] [Full Text] [PDF]

				M. Gallardo and A. Aguilera A New Hyperrecombination Mutation Identifies a Novel Yeast Gene, THP1, Connecting Transcription Elongation With Mitotic Recombination Genetics, January 1, 2001; 157(1): 79 - 89. [Abstract] [Full Text]

				D. Saxe, A. Datta, and S. Jinks-Robertson Stimulation of Mitotic Recombination Events by High Levels of RNA Polymerase II Transcription in Yeast Mol. Cell. Biol., August 1, 2000; 20(15): 5404 - 5414. [Abstract] [Full Text]

				R. Schneiter, C. E. Guerra, M. Lampl, V. Tatzer, G. Zellnig, H. L. Klein, and S. D. Kohlwein A Novel Cold-Sensitive Allele of the Rate-Limiting Enzyme of Fatty Acid Synthesis, Acetyl Coenzyme A Carboxylase, Affects the Morphology of the Yeast Vacuole through Acylation of Vac8p Mol. Cell. Biol., May 1, 2000; 20(9): 2984 - 2995. [Abstract] [Full Text]

				G. Petukhova, S. Van Komen, S. Vergano, H. Klein, and P. Sung Yeast Rad54 Promotes Rad51-dependent Homologous DNA Pairing via ATP Hydrolysis-driven Change in DNA Double Helix Conformation J. Biol. Chem., October 8, 1999; 274(41): 29453 - 29462. [Abstract] [Full Text] [PDF]

				M. Fasullo, J. Koudelik, P. AhChing, P. Giallanza, and C. Cera Radiosensitive and Mitotic Recombination Phenotypes of the Saccharomyces cerevisiae dun1 Mutant Defective in DNA Damage-Inducible Gene Expression Genetics, July 1, 1999; 152(3): 909 - 919. [Abstract] [Full Text]

				F. Paques and J. E. Haber Multiple Pathways of Recombination Induced by Double-Strand Breaks in Saccharomyces cerevisiae Microbiol. Mol. Biol. Rev., June 1, 1999; 63(2): 349 - 404. [Abstract] [Full Text] [PDF]

				R. Schneiter, C. E. Guerra, M. Lampl, G. Gogg, S. D. Kohlwein, and H. L. Klein 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 Mol. Cell. Biol., May 1, 1999; 19(5): 3415 - 3422. [Abstract] [Full Text] [PDF]

				T. Formosa and T. Nittis Dna2 Mutants Reveal Interactions with Dna Polymerase {alpha} and Ctf4, a Pol {alpha} Accessory Factor, and Show That Full Dna2 Helicase Activity Is Not Essential for Growth Genetics, April 1, 1999; 151(4): 1459 - 1470. [Abstract] [Full Text]

				M. Chang, D. French-Cornay, H.-y. Fan, H. Klein, C. L. Denis, and J. A. Jaehning A Complex Containing RNA Polymerase II, Paf1p, Cdc73p, Hpr1p, and Ccr4p Plays a Role in Protein Kinase C Signaling Mol. Cell. Biol., February 1, 1999; 19(2): 1056 - 1067. [Abstract] [Full Text] [PDF]

				Y. Xie, C. Counter, and E. Alani Characterization of the Repeat-Tract Instability and Mutator Phenotypes Conferred by a Tn3 Insertion in RFC1, the Large Subunit of the Yeast Clamp Loader Genetics, February 1, 1999; 151(2): 499 - 509. [Abstract] [Full Text]

				K. J. Gerik, X. Li, A. Pautz, and P. M. J. Burgers Characterization of the Two Small Subunits of Saccharomyces cerevisiae DNA Polymerase delta J. Biol. Chem., July 31, 1998; 273(31): 19747 - 19755. [Abstract] [Full Text] [PDF]

				M. Fasullo, T. Bennett, P. Ahching, and J. Koudelik The Saccharomyces cerevisiae RAD9 Checkpoint Reduces the DNA Damage-Associated Stimulation of Directed Translocations Mol. Cell. Biol., March 1, 1998; 18(3): 1190 - 1200. [Abstract] [Full Text]

				S. Chavez and A. Aguilera The yeast HPR1 gene has a functional role in transcriptional elongation that uncovers a novel source of genome instability Genes & Dev., December 15, 1997; 11(24): 3459 - 3470. [Abstract] [Full Text] [PDF]