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Synthetic rescue

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proteins. It usually means that the deleterious mutation and the suppressive mutation occurs in two residues that are closely located in the tridimensional structure of the multi-protein complex. As thus, this kind of suppression provides indirect information on the molecular structure of the proteins involved.
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Dosage-mediated suppression occurs when the suppression of the mutant phenotype is mediated by the over expression of a second suppressor gene. This can occur when the initial mutations destabilize a protein-protein interaction and over expression of the interacting protein bypass the negative effect
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in the growing polypeptide chain can mutate so that it recognize a TAA stop codon and promote the insertion of serine instead of the termination of the polypeptide chain. This could be particularly useful when a nonsense mutation (TCA >TAA) prevents the expression of a gene by either leading to a
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The strongest form of synthetic rescues, in which the deleterious impact of a gene knockout is mitigated by an additional genetic perturbation that is also deleterious when considered in isolation, was modeled and predicted theoretically for gene interactions mediated by the metabolic network. This
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Interaction-mediated suppression occurs when a deleterious mutation in a component of a protein complex destabilizes the complex. A compensatory mutation in another component of the protein complex can then suppress the deleterious phenotype by re-establishing the interaction between the two
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Puddu, F.; Oelschlaegel, T; Guerini, I; Geisler, NJ; Niu, H; Herzog, M; Salguero, I; Ochoa-Montaño, B; Viré, E; Sung, P; Adams, DJ; Keane, TM; Jackson, SP (2015).
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is rescued ) refers to a genetic interaction in which a cell that is nonviable, sensitive to a specific drug, or otherwise impaired due to the presence of a
123:. The redundancy of tRNA genes makes sure that such mutation would not prevent the normal insertion of serines when the TCA codon specifies them. 84: 35:
becomes viable when the original mutation is combined with a second mutation in a different gene. The second mutation can either be a
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Experimental evolution of diverse Escherichia coli metabolic mutants identifies genetic loci for convergent adaptation of growth rate
319:"Beyond Synthetic Lethality: Charting the Landscape of Pairwise Gene Expression States Associated with Survival in Cancer" 110:
sequence. For example, a tRNA designated for the recognition of the codon TCA and the corresponding insertion of
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Synthetic rescue couples NADPH generation to metabolite overproduction in Saccharomyces cerevisiae
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Motter, Adilson E; Gulbahce, Natali; Almaas, Eivind; Barabási, Albert-László (2008).
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strong form of synthetic rescue has been recently observed in experiments in both
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partially completed polypeptide or degradation of the
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Synthetic rescue could potentially be exploited for
77:Experimental observation of theoretical prediction 290:Partow S. H., Hyland P. B., and Mahadevan K., 8: 237: 235: 344: 334: 267: 215: 189: 307:, PLoS Genetics 14(3), e1007284 (2018). 159: 102:Genetic suppression can be mediated by 7: 106:genes when a mutation alters their 14: 68:Interaction-mediated suppression 39:(equivalent to a knockout) or a 1: 336:10.1016/j.celrep.2019.06.067 54:Types of genetic suppression 294:, Metab. Eng. 43, 64 (2017) 59:Dosage-mediated suppression 396: 178:Molecular Systems Biology 98:tRNA-mediated suppression 64:of the initial mutation. 41:gain-of-function mutation 37:loss-of-function mutation 85:Saccharomyces cerevisiae 260:10.15252/embj.201590973 121:nonsense-mediated decay 303:Wytock T. P. et al., 148:Synthetic lethality 143:Suppressor mutation 25:synthetic viability 329:(4): P938–948.E6. 200:10.1038/msb.2008.1 21:synthetic recovery 317:Magen, A (2019). 254:(11): 1509–1522. 387: 359: 358: 348: 338: 314: 308: 301: 295: 288: 282: 281: 271: 239: 230: 229: 219: 193: 169: 133:Complex networks 91:Escherichia coli 33:genetic mutation 17:Synthetic rescue 395: 394: 390: 389: 388: 386: 385: 384: 365: 364: 363: 362: 316: 315: 311: 302: 298: 289: 285: 241: 240: 233: 171: 170: 161: 156: 129: 100: 79: 70: 61: 56: 12: 11: 5: 393: 391: 383: 382: 377: 367: 366: 361: 360: 309: 296: 283: 231: 158: 157: 155: 152: 151: 150: 145: 140: 135: 128: 125: 99: 96: 78: 75: 69: 66: 60: 57: 55: 52: 27:when a lethal 13: 10: 9: 6: 4: 3: 2: 392: 381: 378: 376: 373: 372: 370: 356: 352: 347: 342: 337: 332: 328: 324: 320: 313: 310: 306: 300: 297: 293: 287: 284: 279: 275: 270: 265: 261: 257: 253: 249: 245: 238: 236: 232: 227: 223: 218: 213: 209: 205: 201: 197: 192: 187: 183: 179: 175: 168: 166: 164: 160: 153: 149: 146: 144: 141: 139: 136: 134: 131: 130: 126: 124: 122: 118: 113: 109: 105: 97: 95: 93: 92: 87: 86: 76: 74: 67: 65: 58: 53: 51: 49: 44: 42: 38: 34: 30: 26: 22: 18: 380:Gene therapy 326: 323:Cell Reports 322: 312: 299: 286: 251: 248:EMBO Journal 247: 181: 177: 138:Gene therapy 101: 89: 83: 80: 71: 62: 48:gene therapy 45: 24: 20: 16: 15: 369:Categories 154:References 208:1744-4292 191:0803.0962 108:anticodon 29:phenotype 375:Genetics 355:31340155 278:25899817 226:18277384 127:See also 346:8261641 269:4474527 217:2267730 184:: 168. 353:  343:  276:  266:  224:  214:  206:  112:serine 88:. and 186:arXiv 351:PMID 274:PMID 222:PMID 204:ISSN 117:mRNA 104:tRNA 19:(or 341:PMC 331:doi 264:PMC 256:doi 212:PMC 196:doi 119:by 23:or 371:: 349:. 339:. 327:28 325:. 321:. 272:. 262:. 252:34 250:. 246:. 234:^ 220:. 210:. 202:. 194:. 180:. 176:. 162:^ 43:. 357:. 333:: 280:. 258:: 228:. 198:: 188:: 182:4

Index

phenotype
genetic mutation
loss-of-function mutation
gain-of-function mutation
gene therapy
Saccharomyces cerevisiae
Escherichia coli
tRNA
anticodon
serine
mRNA
nonsense-mediated decay
Complex networks
Gene therapy
Suppressor mutation
Synthetic lethality



"Predicting synthetic rescues in metabolic networks"
arXiv
0803.0962
doi
10.1038/msb.2008.1
ISSN
1744-4292
PMC
2267730
PMID
18277384

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