genetic suppression


Summary: Mutation process that restores the wild-type PHENOTYPE in an organism possessing a mutationally altered GENOTYPE. The second "suppressor" mutation may be on a different gene, on the same gene but located at a distance from the site of the primary mutation, or in extrachromosomal genes (EXTRACHROMOSOMAL INHERITANCE).

Top Publications

  1. Rutherford S, Villers C, Lee J, Ross W, Gourse R. Allosteric control of Escherichia coli rRNA promoter complexes by DksA. Genes Dev. 2009;23:236-48 pubmed publisher
    ..DksA thus inhibits the transition to RP(I). Our results illustrate in mechanistic terms how transcription factors can regulate initiation promoter-specifically without interacting directly with DNA. ..
  2. Concepcion D, Flores García L, Hamilton B. Multipotent genetic suppression of retrotransposon-induced mutations by Nxf1 through fine-tuning of alternative splicing. PLoS Genet. 2009;5:e1000484 pubmed publisher
  3. Srivatsan A, Han Y, Peng J, Tehranchi A, Gibbs R, Wang J, et al. High-precision, whole-genome sequencing of laboratory strains facilitates genetic studies. PLoS Genet. 2008;4:e1000139 pubmed publisher
  4. Taira H, Matsushita Y, Kojima K, Shiraga K, Hohsaka T. Comprehensive screening of amber suppressor tRNAs suitable for incorporation of non-natural amino acids in a cell-free translation system. Biochem Biophys Res Commun. 2008;374:304-8 pubmed publisher
    ..Further mutagenesis and screening revealed that M. capricolum Trp(1) tRNA with G1C72A73 mutation is the most suitable for efficient and specific incorporation of non-natural amino acids into proteins in response to the amber codon...
  5. Miyata S, Begun J, Troemel E, Ausubel F. DAF-16-dependent suppression of immunity during reproduction in Caenorhabditis elegans. Genetics. 2008;178:903-18 pubmed publisher
    ..The timing of DAF-16-dependent gene activation in sterile mutants coincides with the onset of embryonic development in wild-type animals, suggesting that signals from developing embryos normally downregulate the immune response. ..
  6. Tarailo M, Kitagawa R, Rose A. Suppressors of spindle checkpoint defect (such) mutants identify new mdf-1/MAD1 interactors in Caenorhabditis elegans. Genetics. 2007;175:1665-79 pubmed
    ..elegans. The such-1/APC5-like mutation, h1960, significantly delays anaphase onset both in germline and in early embryonic cells. ..
  7. Zhuang L, Zhang J, Xiang X. Point mutations in the stem region and the fourth AAA domain of cytoplasmic dynein heavy chain partially suppress the phenotype of NUDF/LIS1 loss in Aspergillus nidulans. Genetics. 2007;175:1185-96 pubmed
    ..The fact that a mutation in the end of AAA4 negatively regulates dynein's ATPase activity but partially compensates for NUDF loss indicates the importance of the AAA4 domain in dynein regulation in vivo. ..
  8. Guy C, Atkinson J, Gupta M, Mahdi A, Gwynn E, Rudolph C, et al. Rep provides a second motor at the replisome to promote duplication of protein-bound DNA. Mol Cell. 2009;36:654-66 pubmed publisher
    ..Rep and UvrD therefore provide two contrasting solutions as to how organisms may promote replication of protein-bound DNA. ..
  9. Barkan L, Vijayan P, Carlsson A, Mekhedov S, Browse J. A suppressor of fab1 challenges hypotheses on the role of thylakoid unsaturation in photosynthetic function. Plant Physiol. 2006;141:1012-20 pubmed
    ..Our identification of mutants that suppress the low-temperature phenotype of fab1 provides new tools to understand the relationship between thylakoid lipid structure and photosynthetic function. ..

More Information


  1. Stein K, Davis E, Hays T, Golden A. Components of the spindle assembly checkpoint regulate the anaphase-promoting complex during meiosis in Caenorhabditis elegans. Genetics. 2007;175:107-23 pubmed
    ..These studies provide evidence that components of the spindle assembly checkpoint may regulate the metaphase-to-anaphase transition in the absence of spindle damage during C. elegans meiosis. ..
  2. Fukunaga J, Ohno S, Nishikawa K, Yokogawa T. A base pair at the bottom of the anticodon stem is reciprocally preferred for discrimination of cognate tRNAs by Escherichia coli lysyl- and glutaminyl-tRNA synthetases. Nucleic Acids Res. 2006;34:3181-8 pubmed
    ..coli lysyl- and glutaminyl-tRNA synthetases. ..
  3. Okudaira K, Ohno K, Yoshida H, Asano M, Hirose F, Yamaguchi M. Transcriptional regulation of the Drosophila orc2 gene by the DREF pathway. Biochim Biophys Acta. 2005;1732:23-30 pubmed
    ..The results, taken together, demonstrate that the orc2 gene is under the control of DREF pathway. ..
  4. Zhang C, Roberts T, Yang J, Desai R, Brown G. Suppression of genomic instability by SLX5 and SLX8 in Saccharomyces cerevisiae. DNA Repair (Amst). 2006;5:336-46 pubmed
    ..This suggested that Slx8 and Slx8 played limited roles in stabilizing, restarting, or resolving transiently stalled replication forks, but were critical for preventing the accumulation of DNA damage during normal cell cycle progression. ..
  5. Calonge T, O Connell M. Antagonism of Chk1 signaling in the G2 DNA damage checkpoint by dominant alleles of Cdr1. Genetics. 2006;174:113-23 pubmed
    ..We conclude that regulation of Wee1 by Cdr1 and possibly by related kinases is an important antagonist of Chk1 signaling and represents a novel negative regulation of cell cycle arrest promoted by this checkpoint. ..
  6. Auld K, Hitchcock A, Doherty H, Frietze S, Huang L, Silver P. The conserved ATPase Get3/Arr4 modulates the activity of membrane-associated proteins in Saccharomyces cerevisiae. Genetics. 2006;174:215-27 pubmed
    ..In combination, our characterization of GET3 genetic and biochemical interactions with NPL4, GET1, and GET2 implicates Get3 in multiple membrane-dependent pathways. ..
  7. Sutani T, Kawaguchi T, Kanno R, Itoh T, Shirahige K. Budding yeast Wpl1(Rad61)-Pds5 complex counteracts sister chromatid cohesion-establishing reaction. Curr Biol. 2009;19:492-7 pubmed publisher
    ..Taken together, the presented data suggest that Wpl1-Pds5 complex is inhibitory for cohesion establishment and that Eco1 establishes cohesion by hindering the function of Wpl1-Pds5 temporally in S phase...
  8. Neuburger P, Saville K, Zeng J, Smyth K, Belote J. A genetic suppressor of two dominant temperature-sensitive lethal proteasome mutants of Drosophila melanogaster is itself a mutated proteasome subunit gene. Genetics. 2006;173:1377-87 pubmed
    ..While Prosbeta2(1) shows a modest increase in the number of defective mitotic figures, there were no defects seen with the other two mutants, other than slightly reduced mitotic indexes. ..
  9. Weeks J, Celaya Kolb T, Pecora S, Misra R. AcrA suppressor alterations reverse the drug hypersensitivity phenotype of a TolC mutant by inducing TolC aperture opening. Mol Microbiol. 2010;75:1468-83 pubmed publisher
    ..The results underscore the importance of the periplasmic turn 1 of TolC in the functional assembly of the tripartite efflux complex and AcrA in transitioning TolC from its closed to open state. ..
  10. Zotova L, Aleschko M, Sponder G, Baumgartner R, Reipert S, Prinz M, et al. Novel components of an active mitochondrial K(+)/H(+) exchange. J Biol Chem. 2010;285:14399-414 pubmed publisher
    ..Based on these results, we propose that Ydl183p and the Mdm38p homologues Mrs7p, LETM1, and HCCR-1 are involved in the formation of an active KHE system. ..
  11. Nordman J, Skovgaard O, Wright A. A novel class of mutations that affect DNA replication in E. coli. Mol Microbiol. 2007;64:125-38 pubmed
  12. Fugier C, Tousaint J, Prieur X, Plateroti M, Samarut J, Delerive P. The lipoprotein lipase inhibitor ANGPTL3 is negatively regulated by thyroid hormone. J Biol Chem. 2006;281:11553-9 pubmed
    ..Taken together, our results lead to the identification of ANGPTL3 as a novel TRbeta target gene and provide a new potential mechanism to explain the hypotriglyceridemic properties of TRbeta agonists in vivo. ..
  13. Szabo R, Hobson J, Christoph K, Kosa P, List K, Bugge T. Regulation of cell surface protease matriptase by HAI2 is essential for placental development, neural tube closure and embryonic survival in mice. Development. 2009;136:2653-63 pubmed publisher
    ..This study indicates that unregulated matriptase-dependent cell surface proteolysis can cause a diverse array of abnormalities in mammalian development. ..
  14. Martínez Turiño S, Hernandez C. Inhibition of RNA silencing by the coat protein of Pelargonium flower break virus: distinctions from closely related suppressors. J Gen Virol. 2009;90:519-25 pubmed publisher
    ..Collectively, the results indicate that PFBV CP inhibits RNA silencing by sequestering siRNAs and preventing their incorporation into a RISC, thus behaving similarly to unrelated viral suppressors but dissimilarly to orthologous ones...
  15. De Luca C, Besagni C, Frontali L, Bolotin Fukuhara M, Francisci S. Mutations in yeast mt tRNAs: specific and general suppression by nuclear encoded tRNA interactors. Gene. 2006;377:169-76 pubmed
    ..Finally, we demonstrated, using the RT-PCR method, the existence of significantly variable levels of the TUF1 transcript among strains with functional and dysfunctional mitochondria. ..
  16. Takayama Ito M, Inoue K, Shoji Y, Inoue S, Iijima T, Sakai T, et al. A highly attenuated rabies virus HEP-Flury strain reverts to virulent by single amino acid substitution to arginine at position 333 in glycoprotein. Virus Res. 2006;119:208-15 pubmed
    ..The pathogenicity of rHEP333R to adult mice by intracerebral inoculation largely increased. We confirmed that an arginine at position 333 contributed to reversion of the pathogenicity in a highly attenuated HEP-Flury strain. ..
  17. Perwez T, Hami D, Maples V, Min Z, Wang B, Kushner S. Intragenic suppressors of temperature-sensitive rne mutations lead to the dissociation of RNase E activity on mRNA and tRNA substrates in Escherichia coli. Nucleic Acids Res. 2008;36:5306-18 pubmed publisher
    ..Molecular models of RNase E suggest how suppression may occur. ..
  18. Konstantinidis T, Patsoukis N, Georgiou C, Synetos D. Translational fidelity mutations in 18S rRNA affect the catalytic activity of ribosomes and the oxidative balance of yeast cells. Biochemistry. 2006;45:3525-33 pubmed
    ..In contrast, hyperaccurate mutations rdn1T and rdn2 displayed increased oxidative stress. Our results suggest that the cells may consume more energy to achieve hyperaccuracy leading to increased oxidative modifications. ..
  19. Shimizu M, Murayama N, Nagashima S, Fujieda M, Yamazaki H. Complex mechanism underlying transcriptional control of the haplotyped flavin-containing monooxygenase 3 (FMO3) gene in Japanese: different regulation between mutations in 5'-upstream distal region and common element in proximal region. Drug Metab Pharmacokinet. 2008;23:54-8 pubmed
    ..These results suggest that the putative HNF-4 binding site and CCAAT box could be responsible cis-acting elements of the FMO3 gene in Japanese. ..
  20. Raleigh E, Elbing K, Brent R. Selected topics from classical bacterial genetics. Curr Protoc Mol Biol. 2002;Chapter 1:Unit 1.4 pubmed publisher
    ..Topics include antibiotics, the LAC operon, the F factor, nonsense suppressors, genetic markers, genotype and phenotype, DNA restriction, modification and methylation and recombination. ..
  21. Paschini M, Mandell E, Lundblad V. Structure prediction-driven genetics in Saccharomyces cerevisiae identifies an interface between the t-RPA proteins Stn1 and Ten1. Genetics. 2010;185:11-21 pubmed publisher
    ..We conclude that Stn1 interacts with Ten1 through an alpha-helix, in a manner analogous to the interaction between the comparable subunits of the RPA complex. ..
  22. Giancola S, Rao Y, Chaillou S, Hiard S, Martin Canadell A, Pelletier G, et al. Cytoplasmic suppression of Ogura cytoplasmic male sterility in European natural populations of Raphanus raphanistrum. Theor Appl Genet. 2007;114:1333-43 pubmed
    ..Northern blots and circular RT-PCR analyses showed that orf138 gene expression was impaired in these plants because of a novel cytoplasm-dependent transcript-processing site...
  23. Kang J, Wang L, Giri A, Baldwin I. Silencing threonine deaminase and JAR4 in Nicotiana attenuata impairs jasmonic acid-isoleucine-mediated defenses against Manduca sexta. Plant Cell. 2006;18:3303-20 pubmed
    ..6 mumol) of JA-Ile treatment suggests that TD's defensive role can be attributed more to signaling than to antinutritive defense. ..
  24. Zychlinski D, Erkelenz S, Melhorn V, Baum C, Schaal H, Bohne J. Limited complementarity between U1 snRNA and a retroviral 5' splice site permits its attenuation via RNA secondary structure. Nucleic Acids Res. 2009;37:7429-40 pubmed publisher
    ..The mechanism of 5'ss attenuation was revealed using hyperstable U1 snRNA mutants, showing that restricted U1 snRNP access is the cause of retroviral alternative splicing. ..
  25. Danziger S, Swamidass S, Zeng J, Dearth L, Lu Q, Chen J, et al. Functional census of mutation sequence spaces: the example of p53 cancer rescue mutants. IEEE/ACM Trans Comput Biol Bioinform. 2006;3:114-25 pubmed
    ..92 afterward. Useful mutants were chosen early (overall r = 0.80). Code and data are freely available (, corresponding authors: R.H.L. for computation and R.K.B. for biology). ..
  26. Sasagawa Y, Otani M, Higashitani N, Higashitani A, Sato K, Ogura T, et al. Caenorhabditis elegans p97 controls germline-specific sex determination by controlling the TRA-1 level in a CUL-2-dependent manner. J Cell Sci. 2009;122:3663-72 pubmed publisher
    ..Our results demonstrate that the C. elegans p97/CDC-48-UFD-1-NPL-4 complex controls the sperm-oocyte switch by regulating CUL-2-mediated TRA-1A proteasome degradation. ..
  27. Phan T, Beran R, Peters C, Lorenz I, Lindenbach B. Hepatitis C virus NS2 protein contributes to virus particle assembly via opposing epistatic interactions with the E1-E2 glycoprotein and NS3-NS4A enzyme complexes. J Virol. 2009;83:8379-95 pubmed publisher
    ..These data reveal a complex network of interactions involving NS2 and other viral structural and nonstructural proteins during virus assembly. ..
  28. Sato K, Noda Y, Yoda K. Kei1: a novel subunit of inositolphosphorylceramide synthase, essential for its enzyme activity and Golgi localization. Mol Biol Cell. 2009;20:4444-57 pubmed publisher
    ..From these results, we conclude that Kei1 is essential for both the activity and the Golgi localization of IPC synthase. ..
  29. Marintcheva B, Qimron U, Yu Y, Tabor S, Richardson C, Richardson C. Mutations in the gene 5 DNA polymerase of bacteriophage T7 suppress the dominant lethal phenotype of gene 2.5 ssDNA binding protein lacking the C-terminal phenylalanine. Mol Microbiol. 2009;72:869-80 pubmed publisher
    ..5 lacking the C-terminal phenylalanine. The affected residues map in proximity to aromatic residues and to residues in contact with DNA in the crystal structure of T7 DNA polymerase-thioredoxin. ..
  30. Hanyu Y, Imai K, Kawasaki Y, Nakamura T, Nakaseko Y, Nagao K, et al. Schizosaccharomyces pombe cell division cycle under limited glucose requires Ssp1 kinase, the putative CaMKK, and Sds23, a PP2A-related phosphatase inhibitor. Genes Cells. 2009;14:539-54 pubmed publisher
    ..Ssp1 and Ppe1 thus seem to antagonize in utilizing limited glucose. We also show that Ppk9 and Ssp2 are the catalytic subunits of AMPK and AMPK-related kinases, respectively, which bind to common beta-(Amk2) and gamma-(Cbs2) subunits. ..
  31. Jaenike J. X chromosome drive. Curr Biol. 2008;18:R508-11 pubmed publisher
  32. Doheny J, Mottus R, Grigliatti T. Telomeric position effect--a third silencing mechanism in eukaryotes. PLoS ONE. 2008;3:e3864 pubmed publisher
  33. Li C, Zhao J, Jiang H, Wu X, Sun J, Zhang C, et al. The wound response mutant suppressor of prosystemin-mediated responses6 (spr6) is a weak allele of the tomato homolog of CORONATINE-INSENSITIVE1 (COI1). Plant Cell Physiol. 2006;47:653-63 pubmed
  34. De Lay N, Cronan J. Genetic interaction between the Escherichia coli AcpT phosphopantetheinyl transferase and the YejM inner membrane protein. Genetics. 2008;178:1327-37 pubmed publisher
    ..The mechanism whereby overexpression of a specific cytosolic protein bypasses the essentiality of an inner membrane protein is unknown. ..
  35. D Silva P, Schilke B, Hayashi M, Craig E. Interaction of the J-protein heterodimer Pam18/Pam16 of the mitochondrial import motor with the translocon of the inner membrane. Mol Biol Cell. 2008;19:424-32 pubmed
    ..These data suggest a model in which Tim44 serves as a scaffold for precise positioning of mtHsp70 and its cochaperone Pam18 at the translocon. ..
  36. Song H, Baxter Roshek J, Dinman J, Vakharia V. Efficient expression of the 15-kDa form of infectious pancreatic necrosis virus VP5 by suppression of a UGA codon. Virus Res. 2006;122:61-8 pubmed
    ..Our results demonstrate that the VP5 sequence (with or without a stop codon) yielded approximately 13% termination suppression and the efficiency is directly related to the base immediately 3' of the termination codon, C>A>U>G. ..
  37. Boonsombat R, Yeh S, Milne A, Sandler S. A novel dnaC mutation that suppresses priB rep mutant phenotypes in Escherichia coli K-12. Mol Microbiol. 2006;60:973-83 pubmed
    ..Lastly, we show that dnaC824 is dominant to wild type and that dnaC1331 is recessive to wild type. Several models are discussed for the action of these mutant dnaC proteins in replication restart. ..
  38. Lesch B, Bargmann C. The homeodomain protein hmbx-1 maintains asymmetric gene expression in adult C. elegans olfactory neurons. Genes Dev. 2010;24:1802-15 pubmed publisher
    ..elegans dauer pheromone. ..
  39. Davis M, Jiang J, Zhou J, Freed E, Aiken C. A mutation in the human immunodeficiency virus type 1 Gag protein destabilizes the interaction of the envelope protein subunits gp120 and gp41. J Virol. 2006;80:2405-17 pubmed
    ..Our results suggest that an altered interaction between the MA domain of Gag and the gp41 cytoplasmic tail leads to dissociation of gp120 from gp41 during HIV-1 particle assembly, thus resulting in impaired fusion and infectivity. ..
  40. Ma K, Saha P, Chan L, Moore D. Farnesoid X receptor is essential for normal glucose homeostasis. J Clin Invest. 2006;116:1102-9 pubmed
    ..Taken together, our results identify a link between lipid and glucose metabolism mediated by the FXR-SHP cascade. ..
  41. Espinosa J, Castells M, Laichoubi K, Forchhammer K, Contreras A. Effects of spontaneous mutations in PipX functions and regulatory complexes on the cyanobacterium Synechococcus elongatus strain PCC 7942. Microbiology. 2010;156:1517-26 pubmed publisher
    ..The implications of these results are discussed. ..
  42. Lim H, Vaira A, Reinsel M, Bae H, Bailey B, Domier L, et al. Pathogenicity of Alternanthera mosaic virus is affected by determinants in RNA-dependent RNA polymerase and by reduced efficacy of silencing suppression in a movement-competent TGB1. J Gen Virol. 2010;91:277-87 pubmed publisher
    ..Yeast two-hybrid analysis confirmed that TGB1(P(88)) and TGB1(L(88)) interact. These results identify a TGB1 residue that significantly affects replication and silencing suppression, but maintains full movement functions...
  43. Lee C, Shin Y, Phung T, Bae J, Kang Y, Nguyen T, et al. Involvement of Vts1, a structure-specific RNA-binding protein, in Okazaki fragment processing in yeast. Nucleic Acids Res. 2010;38:1583-95 pubmed publisher
    ..Our results provide both in vivo and in vitro evidence that Vts1 is involved in lagging strand synthesis by modulating the Dna2 endonuclease activity that plays an essential role in Okazaki fragment processing. ..
  44. Schwer B, Shuman S. Genetic analysis of poxvirus mRNA cap methyltransferase: suppression of conditional mutations in the stimulatory D12 subunit by second-site mutations in the catalytic D1 subunit. Virology. 2006;352:145-56 pubmed
  45. O Donnell A, Stevens J, Kepkay R, Barnes C, Johnston G, Singer R. New mutant versions of yeast FACT subunit Spt16 affect cell integrity. Mol Genet Genomics. 2009;282:487-502 pubmed publisher
    ..Thus, the FACT subunit Spt16 and Pkc1 signaling have an overlapping essential function, with an unexpected role for FACT in the maintenance of cell integrity. ..
  46. Chiolo I, Saponaro M, Baryshnikova A, Kim J, Seo Y, Liberi G. The human F-Box DNA helicase FBH1 faces Saccharomyces cerevisiae Srs2 and postreplication repair pathway roles. Mol Cell Biol. 2007;27:7439-50 pubmed
    ..Overall, our findings suggest that the hFBH1 helicase is a functional human orthologue of budding yeast Srs2 that also possesses self-regulation properties necessary to execute its recombination functions. ..
  47. Park H, Davidson E, King M. Overexpressed mitochondrial leucyl-tRNA synthetase suppresses the A3243G mutation in the mitochondrial tRNA(Leu(UUR)) gene. RNA. 2008;14:2407-16 pubmed publisher
    ..This suppression of a tRNA gene mutation by increasing the steady-state levels of its cognate aminoacyl-tRNA synthetase is a model for potential therapies for human pathogenic tRNA mutations. ..
  48. Shema E, Tirosh I, Aylon Y, Huang J, Ye C, Moskovits N, et al. The histone H2B-specific ubiquitin ligase RNF20/hBRE1 acts as a putative tumor suppressor through selective regulation of gene expression. Genes Dev. 2008;22:2664-76 pubmed publisher
    ..Furthermore, frequent RNF20 promoter hypermethylation was observed in tumors. RNF20 may thus be a putative tumor suppressor, acting through selective regulation of a distinct subset of genes. ..
  49. Ukil L, Varadaraj A, Govindaraghavan M, Liu H, Osmani S. Copy number suppressors of the Aspergillus nidulans nimA1 mitotic kinase display distinctive and highly dynamic cell cycle-regulated locations. Eukaryot Cell. 2008;7:2087-99 pubmed publisher
    ..Three sites of MCNA phosphorylation were mapped and mutated to implicate proline-directed phosphorylation in the equal segregation of MCNA during the cell cycle. The data indicate all three MCN proteins likely have cell cycle functions. ..
  50. Aguilar Fuentes J, Fregoso M, Herrera M, Reynaud E, Braun C, Egly J, et al. p8/TTDA overexpression enhances UV-irradiation resistance and suppresses TFIIH mutations in a Drosophila trichothiodystrophy model. PLoS Genet. 2008;4:e1000253 pubmed publisher
    ..This study is the first using an intact higher-animal model to show that one subunit mutant can trans-complement another subunit in a multi-subunit complex linked to human diseases. ..
  51. Shin B, Kim J, Acker M, Maher K, Lorsch J, Dever T. rRNA suppressor of a eukaryotic translation initiation factor 5B/initiation factor 2 mutant reveals a binding site for translational GTPases on the small ribosomal subunit. Mol Cell Biol. 2009;29:808-21 pubmed publisher
  52. Iraha F, Oki K, Kobayashi T, Ohno S, Yokogawa T, Nishikawa K, et al. Functional replacement of the endogenous tyrosyl-tRNA synthetase-tRNATyr pair by the archaeal tyrosine pair in Escherichia coli for genetic code expansion. Nucleic Acids Res. 2010;38:3682-91 pubmed publisher
    ..The present engineering allows E. coli TyrRS variants for non-natural amino acids to be developed in E. coli, for use in both eukaryotic and bacterial cells for genetic code expansion...