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Cell death resulting from a deficiency of or interaction between in two or more genes
Synthetic lethality is defined as a type of genetic interaction where the combination of two genetic events results in cell death or death of an organism
Synthetic_lethality
DNA topoisomerase enzyme
benefit when administered to treat patients with a KRAS mutant tumor. Synthetic lethality arises when a combination of deficiencies in the expression of two
TOP1
term synthetic rescue is derived from synthetic lethality, where the combination of two mutations leads to cell death (whereas neither alone is lethal).
Synthetic_rescue
Medical intervention
care practitioners with exercise prescription in cancer patients. Synthetic lethality arises when a combination of deficiencies in the expression of two
Cancer_treatment
Sub-field of genomics
may be the untapped reservoir for then pursuing a synthetic lethality approach. Collateral lethality therefore holds great potential in identification
Oncogenomics
expanding our knowledge of genetic interactions. Synthetic genetic arrays (SGA), diploid based synthetic lethality analysis on microarrays (dSLAM), and epistatic
Epistasis and functional genomics
Epistasis_and_functional_genomics
Compounds that inhibit the activity of DNA topoisomerases
appeared to be especially synthetically lethal with deficient WRN expression. Further evaluations have also indicated synthetic lethality of deficient expression
Topoisomerase_inhibitor
Synthetic genetic array analysis (SGA) is a high-throughput technique for exploring synthetic lethal and synthetic sick genetic interactions (SSL). SGA
Synthetic_genetic_array
Class of enzymes
topoisomerase I activity during infection to ensure optimal phage yield. Synthetic lethality arises when a combination of deficiencies in the expression of two
Type_I_topoisomerase
Research tool in genomics
Tang M, et al. (April 2019). "Genome-wide CRISPR screens reveal synthetic lethality of RNASEH2 deficiency and ATR inhibition". Oncogene. 38 (14): 2451–2463
Genome-wide CRISPR-Cas9 knockout screens
Genome-wide_CRISPR-Cas9_knockout_screens
Gene thought to be critical for an organism's survival
Nieuwenhuis J, Staring J, et al. (November 2015). "Gene essentiality and synthetic lethality in haploid human cells". Science. 350 (6264): 1092–6. Bibcode:2015Sci
Essential_gene
Chemical compound
suppressor gene PTEN. In PTEN-deficient tumors, leflunomide causes synthetic lethality potentially due to increased demand on pyrimidines in these faster
Leflunomide
Condition of genetic hypermutability
S, Voest EE, Bardelli A, Garnett MJ (2021). "Werner Helicase Is a Synthetic-Lethal Vulnerability in Mismatch Repair-Deficient Colorectal Cancer Refractory
Microsatellite_instability
Phenotypically-different organism resulting from a mutation
Genetically modified organism Mutants in fiction Mutationism Synthetic lethality Synthetic viability Egener et al. BMC Plant Biology 2002 2:6 doi:10.1186/1471-2229-2-6
Mutant
Dependence of a gene mutation's phenotype on mutations in other genes
epistasis. When two mutations are viable alone but lethal in combination, it is called Synthetic lethality or unlinked non-complementation. In a haploid organism
Epistasis
of diverse cancer types, platinum and PARP inhibitor to exploit synthetic lethality in homologous recombination deficient breast cancer). The biological
Mutational_signatures
Cellular mechanism
the latter approach has been termed 'synthetic lethality'. Perhaps the most well-known of these 'synthetic lethality' drugs is the poly(ADP-ribose) polymerase
DNA_repair
Chromatin remodeling complex
Hargreaves, Diana C (2 October 2017). "Chromatin accessibility underlies synthetic lethality of SWI/SNF subunits in ARID1A-mutant cancers". eLife. 6 e30506. doi:10
Mammalian SWI/SNF (BAF) complex
Mammalian_SWI/SNF_(BAF)_complex
inhibitors optimally. PARP inhibitors operate on the concept of synthetic lethality by selectively causing cell death in BRCA-mutant cells while sparing
HRDetect
Bacterium that causes tuberculosis
Given that Rv2156c is involved in peptidoglycan synthesis, this synthetic lethality could be exploited to sensitize M. tuberculosis to β-lactam antibiotics
Mycobacterium_tuberculosis
Chemical compound
European Union and Russia under the brand name Livazo.[citation needed] Synthetic lethality has been demonstrated in mice with triple-negative breast cancer
Pitavastatin
Designer drugs
Synthetic cannabinoids, or neocannabinoids, are a class of designer drug molecules that bind to the same receptors to which cannabinoids (THC, CBD and
Synthetic_cannabinoids
Chemical compound
clinical trials. It inhibits both PARP1 and PARP2 and thereby induces synthetic lethality. It is still being evaluated for the treatment of ovarian cancer
Veliparib
Organic compound (H–CHO); simplest aldehyde
formaldehyde catabolism enzymes (ADH5 and ALDH2) leads to partial synthetic lethality in C57BL/6 mice". Genes and Environment. 42 (1): 21. Bibcode:2020GeneE
Formaldehyde
Genetic recombination between identical or highly similar strands of genetic material
inhibiting BER in an HR-deficient cell, olaparib applies the concept of synthetic lethality to specifically target cancer cells. While PARP1 inhibitors represent
Homologous_recombination
Investigational drug
Shah PA, Arbour KC (April 2026). "MTAP Deletion in Oncogenesis: A Synthetic Lethality Scenario". Cancer Research. 86 (7): 1558–1569. doi:10.1158/0008-5472
Anvumetostat
Field of molecular biology
of multi-protein complexes. This approach can be used to identify synthetic lethality by using the appropriate genetic background. CRISPRi and CRISPRa
Functional_genomics
Field of study
loss-of-function mutations can be targeted by drugs that induce synthetic lethality, a genetic/protein interaction where the loss of one component induces
Pharmacoepigenetics
Pharmacological enzyme inhibitors of poly (ADP-ribose) polymerases
PMID 12415303. Lord CJ, Ashworth A (March 2017). "PARP inhibitors: Synthetic lethality in the clinic". Science. 355 (6330): 1152–8. Bibcode:2017Sci...355
PARP_inhibitor
selectively killed to abrogate virus production using the concept of synthetic lethality. Aitchison and his colleagues have also developed a cohort of nanobodies
John_D._Aitchison
French researcher, oncologist
as part of the team of Alan Ashworth, focusing on DNA repair and synthetic lethality. She completed her post-doctoral fellowship in Paris and spent 18
Sophie_Postel-Vinay
American biologist
Shokhirev MN, Benner C, Hargreaves DC. Chromatin accessibility underlies synthetic lethality of SWI/SNF subunits in ARID1A-mutant cancers. Elife. 2017 Oct 2;6
Diana_Hargreaves
Protein-coding gene in humans
Fang B (September 2008). "Identification of a small molecule with synthetic lethality for K-ras and protein kinase C iota". Cancer Research. 68 (18): 7403–7408
KRAS
Weapon less likely to kill a target
live ammunition at crowds. In the late 1980s and early 1990s, the Non-lethality Policy Review Group at U.S. Global Strategy Council in Washington and
Non-lethal_weapon
Human gene database maintained by the Weizmann Institute of Science
GeneCard. Another example is a research study on synthetic lethality in cancer. Synthetic lethality appears when a mutation in a single gene has no effect
GeneCards
Protein-coding gene in the species Homo sapiens
mutations of Gen1 and Eme1 were combined in mice the result was synthetic lethality at an early embryonic stage. Homozygosity for Gen1 mutations did
EME1
American biochemist
a Whitehead Fellow at the Whitehead Institute, where he worked on synthetic lethal screens and cell death. In 2003, he developed the first library of
Brent_Stockwell
American researcher
the first time used the term synthetic lethality in the modern sense of two non-lethal mutations resulting in lethality in the double mutant. Stearns
Tim_Stearns
Chemical compound (cancer therapy drug)
2017. Retrieved 11 June 2019. "Olaparib: realising the promise of synthetic lethality". Cancer Research UK. 16 July 2015. "PARP inhibitors: Halting cancer
Olaparib
Process that prevents the expression of a gene
is also currently being used in drug discovery efforts, such as synthetic lethality, high-throughput screening, and miniaturized RNAi screens.[citation
Gene_silencing
Pharmaceutical compound
Ferrandi G, Rinaldi F, Myers SH, et al. (July 2024). "New Horizons of Synthetic Lethality in Cancer: Current Development and Future Perspectives". Journal
Lunresertib
British cancer researcher and oncologist
Meeting, Radiation Research Society, Oceans of Opportunity" (PDF). Synthetic Lethality and Repair Targeting: New Opportunities for Treatment. Radiation
Simon_N._Powell
Mammalian protein found in Homo sapiens
C, Petermann E, et al. (February 2016). "ATR inhibition induces synthetic lethality and overcomes chemoresistance in TP53- or ATM-defective chronic lymphocytic
ATM_serine/threonine_kinase
Class of proteins
14.2164. PMC 317009. PMID 9679061. Onodera, K (2000). "Perinatal synthetic lethality and hematopoietic defects in compound mafG::mafK mutant mice". EMBO
Small_Maf
Type of programmed cell death
2003). "Identification of genotype-selective antitumor agents using synthetic lethal chemical screening in engineered human tumor cells". Cancer Cell. 3
Ferroptosis
Protein-coding gene in the species Homo sapiens
F, Zang C, Pons M, et al. (March 2022). "NOXA expression drives synthetic lethality to RUNX1 inhibition in pancreatic cancer". Proceedings of the National
Phorbol-12-myristate-13-acetate-induced protein 1
Phorbol-12-myristate-13-acetate-induced_protein_1
Chemical compound
2018). "Combined Erlotinib and PF-03084014 treatment contributes to synthetic lethality in head and neck squamous cell carcinoma". Cell Proliferation. 51
Nirogacestat
Molecule initiating ferroptotic cell death
2003). "Identification of genotype-selective antitumor agents using synthetic lethal chemical screening in engineered human tumor cells". Cancer Cell. 3
Erastin
U.S. health institute
Barrett's Esophagus Translational Research Network, New Approaches to Synthetic Lethality for Mutant KRAS-Dependent Cancers, Molecular and Cellular Characterization
National_Cancer_Institute
Form of biological modelling
network and the synthetic accessibility metric is recalculated. An increase in the total number of steps is predicted to cause lethality. Wunderlich and
Metabolic_network_modelling
Protein-coding gene in Homo sapiens
ENO1-homozygously deleted cancer cells constitutes an example of synthetic lethality treatment for cancer. ENO1 has been detected in serum drawn from
Alpha-enolase
Family of proteins
homologous recombination repair (HRR) is defective, and leading to the synthetic lethality of PARP inhibitors in HRR-defective cancer. HRR defects are classically
Poly_(ADP-ribose)_polymerase
Human DNA protein
serine/threonine-specific protein kinase family of enzymes. STK33 was identified as a synthetic lethal gene in KRAS-dependent cell lines. STK33 has been considered as a target
STK33
Enzyme involved in glycolysis
deletion of the ENO1 gene as part of the 1p36 tumor suppressor locus (synthetic lethality). A natural product phosphonate antibiotic, SF2312 (CAS 107729-45-3)
Enolase
of the double mutant is stronger than expected. A special case is a synthetic lethal interaction which occurs when the removal of individual genes does
Genetic_interaction_network
Enzyme found in humans
seen in Werner syndrome. Recently, WRN has been identified as a synthetic lethality target in cancers containing a high number of microsatellites. These
Werner_syndrome_helicase
Evolutionary biology hypothesis
its removal is not inherently lethal, however when the gene and its redundancy are removed, the result is lethality. Computational simulations of knockouts
Evolutionary_capacitance
Protein-coding gene in humans
D'Angiolella V (August 2019). "E2F1 proteolysis via SCF-cyclin F underlies synthetic lethality between cyclin F loss and Chk1 inhibition". The EMBO Journal. 38
CCNF
Investigational drug
et al. (February 2022). "Fragment-Based Discovery of MRTX1719, a Synthetic Lethal Inhibitor of the PRMT5•MTA Complex for the Treatment of MTAP-Deleted
Navlimetostat
British biologist
Society's Mullard Award for his research on DNA repair mechanisms and synthetic lethality that led to the discovery of olaparib which has reached blockbuster
Stephen_Jackson_(biologist)
Polish Professor of biological sciences
Piwocka K, Prochorec-Sobieszek M, Mikula M, and Miączyńska M. (2020) Synthetic lethality between VPS4A and VPS4B triggers an inflammatory response in colorectal
Marta_Miączyńska
of embryonic development and cell growth Many, including nucleus Synthetic lethality BioGRID Heterogenous Ribonucleoprotein L (HBRNPL) Nucelocytoplasmic
LUZP2
Chemical compound
silencing of DNA repair genes active in alternative pathways (see synthetic lethality). In a phase 1 trial to determine dosing in patients with AML and
Pevonedistat
Medical condition
(including immunotherapy such as monoclonal antibody therapy) and synthetic lethality, most commonly as a series of separate treatments (e.g. chemotherapy
Signs_and_symptoms_of_cancer
Protein-coding gene in humans
F, Zang C, Pons M, et al. (March 2022). "NOXA expression drives synthetic lethality to RUNX1 inhibition in pancreatic cancer". Proceedings of the National
RUNX1
Gene found in fruit flies
first two Smad genes discovered. For both genes, the maternal effect lethality was the basis for the selection of their names. Medea was named for the
Medea_gene
Protein complex that regulates the separation of sister chromatids during cell division
D.; Horsfield, Julia A. (7 December 2020). "Cohesin mutations are synthetic lethal with stimulation of WNT signaling". eLife. 9 e61405. doi:10.7554/eLife
Cohesin
Protein-coding gene in the species Homo sapiens
pathway, causes a second repair pathway to be deficient leading to synthetic lethality. GRCh38: Ensembl release 89: ENSG00000168496 – Ensembl, May 2017
Flap structure-specific endonuclease 1
Flap_structure-specific_endonuclease_1
Chemical compound
diabetic drug metformin is strongly potentiated by syrosingopine. Synthetic lethality elicited by combining the two drugs is synergistic and specific to
Syrosingopine
Protein-coding gene in the species Homo sapiens
had homozygous mutations for both Gen1 and Eme1, they exhibited synthetic lethality at an early embryonic stage. Gen1 mutant homozygosity, alone, in
GEN1, Holliday junction 5' flap endonuclease
GEN1,_Holliday_junction_5'_flap_endonuclease
Protein-coding gene in the species Homo sapiens
local replication stress at telomeres — CHAMP1 deficiency creates synthetic lethality with inhibition of the FANCM translocase. Independently, the CHAMP1
CHAMP1
Protein-coding gene
Shavit JA, Motohashi H, Yamamoto M, Engel JD (Mar 2000). "Perinatal synthetic lethality and hematopoietic defects in compound mafG::mafK mutant mice". The
MAFF_(gene)
Cells cultured for medical research
Cancer therapy Plasmid Recombinant AAV mediated genome engineering Synthetic lethality Zinc finger nuclease Torrance CJ, Agrawal V, Vogelstein B, Kinzler
Isogenic_human_disease_models
Protein found in humans
Elledge, S. J. (2009). "A genome-wide RNAi screen identifies multiple synthetic lethal interactions with the Ras oncogene". Cell. 137 (5): 835–848. doi:10
Chromosome 4 open reading frame 54
Chromosome_4_open_reading_frame_54
Protein-coding gene in humans
treatment with Chk1 inhibition enhances targeted cell death and provides synthetic lethality. Many cancers rely on Chk1 mediated cell cycle arrest heavily, especially
CHEK1
Protein-coding gene in the species Homo sapiens
Liu J, Fang B (Sep 2008). "Identification of a small molecule with synthetic lethality for K-ras and protein kinase C iota". Cancer Research. 68 (18): 7403–8
PRKCI
Protein involved in DNA repair
Carley AC, Tchang B, Powell SN (July 2013). "RAD52 inactivation is synthetically lethal with deficiencies in BRCA1 and PALB2 in addition to BRCA2 through
RAD51
Data scientist, developer of R software
animal Caenorhabditis elegans to test genetic interactions causing synthetic lethality in somatic cells, and a novel yeast-based model to search for modifier
Jenny_Bryan
Protein-coding gene in the species Homo sapiens
damages than non-cancerous cells without a RAD54 defect (see article Synthetic lethality). GRCh38: Ensembl release 89: ENSG00000197275 – Ensembl, May 2017
RAD54B
Medical condition
MacKenzie ED, Jerby L, et al. (August 2011). "Haem oxygenase is synthetically lethal with the tumour suppressor fumarate hydratase". Nature. 477 (7363):
Hereditary leiomyomatosis and renal cell cancer syndrome
Hereditary_leiomyomatosis_and_renal_cell_cancer_syndrome
Hollow-point bullet tipped with a polymer nose cone
hollow point upon impact, causing the bullet to expand, which increases lethality. These bullets are typically designed for rifles and single-shot handguns
Plastic-tipped_bullet
Protein-coding gene in the species Homo sapiens
inactivation in small cell lung cancer disrupts MYC-SWI/SNF programs and is synthetic lethal with BRG1". Cancer Discov. 4 (3): 292–303. doi:10.1158/2159-8290.CD-13-0799
MAX_dimerization_protein_MGA
Class of drug
term opioid is often used to designate all substances, both natural and synthetic, that bind to opioid receptors in the brain, while the term opiate is
Opioid
Protein-coding gene in the species Homo sapiens
silencing of DNA repair genes active in alternative pathways (see synthetic lethality). In a phase 1 trial of Pevonedistat to determine dosing in patients
APPBP1
Biological lab technique
Another important variant is the synthetic-lethal screen, which looks for mutation pairs that are viable individually but lethal in combination and can reveal
Genetic_screen
Elledge SJ (May 2009). "A genome-wide RNAi screen identifies multiple synthetic lethal interactions with the Ras oncogene". Cell. 137 (5): 835–48. doi:10
Disease_gene_identification
Evolution of novel genes from non-genic DNA sequence
expressed at both the mRNA and protein levels, and when deleted is synthetically lethal with two other yeast genes, all of which indicate a functional role
De_novo_gene_birth
Protein-coding gene in the species Homo sapiens
et al. (February 2022). "Fragment-Based Discovery of MRTX1719, a Synthetic Lethal Inhibitor of the PRMT5•MTA Complex for the Treatment of MTAP-Deleted
Protein arginine methyltransferase 5
Protein_arginine_methyltransferase_5
Protein-coding gene in the species Homo sapiens
GG, Guo G, Pandita TK, Powell SN (2011). "Rad52 inactivation is synthetically lethal with BRCA2 deficiency". Proc. Natl. Acad. Sci. U.S.A. 108 (2): 686–91
RAD52
Protein-coding gene in humans
specifically in Max-deficient cells, suggesting that the two together cause synthetic lethality. Furthermore, Max required BRG1 to activate neuroendocrine transcriptional
MAX_(gene)
Rush; music: Hans Swarowsky & Vienna Symphony color 11m October 9, 1956 Synthetic Fibers: Nylon and Rayon Malcolm Dole B&W 14m December 9, 1949 video [852]
List of Encyclopædia Britannica Films titles
List_of_Encyclopædia_Britannica_Films_titles
Protein-coding gene in the species Homo sapiens
Liu JL (March 2022). "Combined Inactivation of CTPS1 and ATR Is Synthetically Lethal to MYC-Overexpressing Cancer Cells". Cancer Research. 82 (6): 1013–1024
CTP_synthase_1
Protein-coding gene in the species Homo sapiens
Shavit JA, Motohashi H, Yamamoto M, Engel JD (Mar 2000). "Perinatal synthetic lethality and hematopoietic defects in compound mafG::mafK mutant mice". The
MAFK
Group of methods in synthetic biology
simply gene synthesis, refers to a group of methods that are used in synthetic biology to construct and assemble genes from nucleotides de novo. Unlike
Artificial_gene_synthesis
Protein found in the human body
silencing of DNA repair genes active in alternative pathways (see synthetic lethality). Pevonedistat (MLN4924), a drug inhibiting activation of NEDD8,
NEDD8
Chemical compound
a direct and potent antagonist of membrane-restricted Mcl-1 and is synthetic lethal with treatment that induces Bim". BMC Cancer. 15: 568. doi:10.1186/s12885-015-1582-5
Obatoclax
Protein-coding gene in the species Homo sapiens
Shavit JA, Motohashi H, Yamamoto M, Engel JD (Mar 2000). "Perinatal synthetic lethality and hematopoietic defects in compound mafG::mafK mutant mice". The
MAFG
Type of firearm
In current usage, a riot gun or less-lethal launcher is a type of firearm used to fire "non-lethal" or "less-lethal" ammunition for the purpose of suppressing
Riot_gun
Chemical compound
Konieczkowski, David J.; Liu, David (2021-04-01). "Identification of a Synthetic Lethal Relationship between Nucleotide Excision Repair Deficiency and Irofulven
Irofulven
its role as a G1 cell cycle regulator. For example, BCK2-null is synthetically lethal with G1 cyclin CLN3, and leads to a decrease in mRNA levels of another
BCK2
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