Human Disease Model Report: cancer, epithelial, compromised apoptosis and DNA repair defects

General Information

Name

cancer, epithelial, compromised apoptosis and DNA repair defects

FlyBase ID

FBhh0001053

Disease Ontology Term

carcinoma

Parent Disease

OMIM

Overview

In a background of apoptosis-deficient cells in imaginal discs, X-irradiation results in tumorigenic phenotypes, including overgrowth of targeted cells within the disc and delamination of the epithelium (see FBhh0001040). The additional effects of reduced function of genes involved in DNA repair have been assessed. RNAi-mediated reduction of okr (orthologous to human RAD54L) or spn-A (orthologous to human RAD51) enhance the tumorigenic phenotypes; these genes are required for homologous recombination repair of DNA double-strand breaks in G2. In contrast, loss-of-function mutation of a gene required for nonhomologous end-joining repair in G1, the ligase DNAlig4, has no effect.

[updated Jun. 2019 by FlyBase; FBrf0222196]

Disease Summary Information

Disease Summary: cancer, epithelial, compromised apoptosis and DNA repair defects

OMIM report

Human gene(s) implicated

Symptoms and phenotype

Genetics

Cellular phenotype and pathology

Molecular information

External links

KEGG Disease Pathways: Pathways in Cancer

Disease synonyms

Related Diseases

Related human health report(s)

cancer, epithelial, compromised apoptosis

Ortholog Information

Human gene(s) in FlyBase

Other mammalian ortholog(s) used

D. melanogaster Gene Information (2)

Dmel\okr

Gene Snapshot

okra (okr) encodes a helicase involved in homologous DNA repair. It functions in meiotic recombination. [Date last reviewed: 2019-03-14]

Molecular function (GO)

Cellular component (GO)

nucleus

Gene Groups / Pathways

SNF2

Comments on ortholog(s)

High-scoring ortholog of human RAD54L (multiple in both species). Dmel\okr shares 55% identity and 72% similarity with human RAD54L. Dmel\okr shares 39% identity and 56% similarity with the low-scoring human ortholog RAD54B.

Orthologs and Alignments from DRSC

DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans

H. sapiens (Human)

Dmel\spn-A

Gene Snapshot

spindle A (spn-A) encodes a protein that forms a filament on single-stranded DNA, does a homology search of double-stranded DNA, and catalyzes strand exchange, swapping the single-strand DNA in and displacing the partner of the complementary strand. [Date last reviewed: 2019-03-14]

Molecular function (GO)

Cellular component (GO)

condensed nuclear chromosome

Gene Groups / Pathways

RAD51

Comments on ortholog(s)

High-scoring ortholog of human RAD51 (multiple in both species). Dmel\spn-A shares 63% identity and 76% similarity with the human gene.

Orthologs and Alignments from DRSC

DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans

H. sapiens (Human)

Other Genes Used: Viral, Bacterial, Synthetic (1)

BacA\p35

Summary of Physical Interactions (5 groups)

spn-A

protein-protein

Interacting group

Assay

References

spn-A - Brca2

anti tag coimmunoprecipitation, anti tag western blot, ion exchange chromatography, peptide massfingerprinting

(Kusch, 2015, Brough et al., 2008)

spn-A - flfl

pull down, Identification by mass spectrometry, autoradiography

(Karman et al., 2020)

spn-A - RecQ5

two hybrid, anti tag coimmunoprecipitation, anti tag western blot, pull down, autoradiography

(Maruyama et al., 2012)

spn-A - Rrp6

proximity ligation assay, fluorescence microscopy, anti bait coimmunoprecipitation, anti tag western blot

(Marin-Vicente et al., 2015)

BacA\p35

protein-protein

Interacting group

Assay

References

BacA\p35 - Dredd

anti tag coimmunoprecipitation, anti tag western blot

(Guntermann and Foley, 2011)

Alleles Reported to Model Human Disease (Disease Ontology) (8 alleles)

okr

Models Based on Experimental Evidence ( 1 )

Allele

Disease

Evidence

References

okr^KK107487

model of cancer

CEA with BacA\p35^UAS.cHa

(Dekanty et al., 2015)

Modifiers Based on Experimental Evidence ( 2 )

Allele

Disease

Interaction

References

okr^RU

ameliorates Bloom syndrome

modeled by Blm^D2, Blm^N1

(Lafave et al., 2014)

okr^KK107487

model of cancer

is ameliorated by bsk^K53R.UAS

(Dekanty et al., 2015)

spn-A

Models Based on Experimental Evidence ( 0 )

Allele

Disease

Evidence

References

Modifiers Based on Experimental Evidence ( 1 )

Allele

Disease

Interaction

References

spn-A^093A

ameliorates Bloom syndrome

modeled by Blm^D2, Blm^N1

(Lafave et al., 2014)

BacA\p35

Models Based on Experimental Evidence ( 1 )

Allele

Disease

Evidence

References

BacA\p35^UAS.cHa

model of cancer

CEA with okr^KK107487

(Dekanty et al., 2015)

CEA with grp^GD4189

(Dekanty et al., 2015)

CEA with grp^KK108548

(Dekanty et al., 2015)

CEA with mei-41^GD4258

(Dekanty et al., 2015)

CEA with mei-41^KK101792

(Dekanty et al., 2015)

CEA with hid^UAS.cUa

(Rudrapatna et al., 2013)

CEA

(Perez-Garijo et al., 2004)

CEA with Bub3^GD9924

(Muzzopappa et al., 2017)

CEA with rod^GD8768

(Muzzopappa et al., 2017)

CEA with mud^HMS01458

(Muzzopappa et al., 2017)

CEA with Ras85D^V12.UAS

(Khalili et al., 2023)

model of carcinoma

CEA with Vps25^Pb2931

(Thompson et al., 2005)

CEA with hep^Act.UAS

(Uhlirova and Bohmann, 2006)

Modifiers Based on Experimental Evidence ( 5 )

Allele

Disease

Interaction

References

BacA\p35^GMR.PH

ameliorates tauopathy

modeled by Hsap\MAPT^GMR.Ex.PJ

(Jackson et al., 2002)

ameliorates retinal disease

modeled by norpA^EE5

(Chinchore et al., 2012)

ameliorates cancer

modeled by Alk^UAS.cLa

(Wolfstetter et al., 2020)

ameliorates ataxia telangiectasia

modeled by tefu^RNAi.UAS

(Rimkus et al., 2008)

BacA\p35^UAS.cHa

exacerbates cancer

modeled by Bub3^GD9924

(Barrio et al., 2023)

exacerbates brain cancer

modeled by l(3)mbt^GD4370, l(3)mbt^ts1

(Climent-Cantó et al., 2022)

ameliorates Alzheimer's disease

modeled by Tom40^{UAS.Tag:FLAG,Tag:HA}

(Periasamy et al., 2022)

ameliorates Alzheimer's disease 1

modeled by Hsap\APP^{Aβ42.QUAS.Tag:SS(nec)}

(Sheng et al., 2023)

ameliorates tauopathy

modeled by Hsap\MAPT^{T231A.S235A.UAS}

(Steinhilb et al., 2007)

modeled by Hsap\MAPT^{S396A.S404A.UAS}

(Steinhilb et al., 2007)

modeled by Hsap\MAPT^{S202A.T205A.UAS}

(Steinhilb et al., 2007)

modeled by Hsap\MAPT^UAS.cWa

(Steinhilb et al., 2007)

ameliorates amyotrophic lateral sclerosis

modeled by Hsap\TARDBP^UAS.YFP.cEa

(Estes et al., 2011)

modeled by Hsap\TARDBP^{A315T.UAS.YFP}

(Estes et al., 2011)

ameliorates neurodegenerative disease

modeled by Hsap\ATXN3^{tr.Q78.UAS.Tag:HA}

(Wong et al., 2008)

ameliorates microcephaly

modeled by mad2^G6595, Sas-4^s2214

(Poulton et al., 2017)

exacerbates carcinoma

modeled by scrib¹

(Zheng et al., 2023, Brumby and Richardson, 2003)

modeled by l(2)gl⁴

(Rusu et al., 2021)

ameliorates retinitis pigmentosa 4

modeled by ninaE^P37H

(Galy et al., 2005)

ameliorates human immunodeficiency virus infectious disease

modeled by HIV-1\Vpu^UAS.cLa

(Marchal et al., 2012)

ameliorates myotonia congenita

modeled by mst^JF03280

(Min et al., 2017)

ameliorates cancer

modeled by Ras85D^V12.UAS, scrib⁶⁷³

(Pérez et al., 2017)

BacA\p35^UAS.cUa

ameliorates gastrointestinal adenoma

modeled by Apc^Q8, Apc2^g10

(Suijkerbuijk et al., 2016)

ameliorates cytochrome-c oxidase deficiency disease

modeled by Scox^GD898

(Martínez-Morentin et al., 2015)

exacerbates cancer

modeled by Hsap\CDH3^UASp.cPa

(Faria et al., 2023)

ameliorates autosomal dominant cerebellar ataxia

modeled by Hsap\ATXN1^82.UAS

(Ghosh and Feany, 2004)

modeled by Hsap\ATXN3^{tr.Q78.UAS.Tag:HA}

(Ghosh and Feany, 2004)

exacerbates carcinoma

modeled by Delta^UAS.cDa, lola^GS88A8

(Pérez et al., 2015)

ameliorates myotonic dystrophy type 2

modeled by Zzzz\CCTG^UAS.106

(Yenigun et al., 2017)

ameliorates severe acute respiratory syndrome

modeled by HCoV-SARS\3a^{UAS.CUHK-W1.EGFP}

(Wong et al., 2005)

ameliorates Alzheimer's disease 1

modeled by Hsap\APP^{3-42.E3Q.UAS.Tag:SS(rPENK)}

(Tsuda et al., 2017)

ameliorates cancer

modeled by Egfr^UAS.cBa, mir-8^UAS.cUa

(Eichenlaub et al., 2016)

ameliorates Coronavirus infectious disease

modeled by HCoV-SARS\M^{UAS.CUHK-Su10}

(Chan et al., 2007)

exacerbates Alexander disease

modeled by Hsap\GFAP^R79H.UAS

(Wang et al., 2022)

BacA\p35^lexAop.cEa

ameliorates juvenile polyposis syndrome

modeled by shn^KK101278

(Zhou et al., 2021)

BacA\p35^QUAS.cPGa

ameliorates Huntington's disease

modeled by Hsap\HTT^{Q25.ex1.UAS.GFP}, Hsap\HTT^{Q91.ex1.QUAS.mCherry}

(Donnelly et al., 2020)

Alleles Representing Disease-Implicated Variants

Genetic Tools, Stocks and Reagents

Sources of Stocks

Contact lab of origin for a reagent not available from a public stock center.

Bloomington Stock Center Disease Page

Related mammalian, viral, bacterial, or synthetic transgenes

Allele

Transgene

Publicly Available Stocks

BacA\p35^{UASp.Tag:FLAG}

P{UASp-p35.Flag}

Selected Drosophila transgenes

Allele

Transgene

Publicly Available Stocks

RNAi constructs available

Allele

Transgene

Publicly Available Stocks

okr^GD4181

P{GD4181}

w¹¹¹⁸; P{GD4181}v30472/TM3

y¹ v¹; P{TRiP.JF01286}attP2

okr^JF01494

P{TRiP.JF01494}

y¹ v¹; P{TRiP.JF01494}attP2

okr^HMS00585

P{TRiP.HMS00585}

y¹ sc^* v¹ sev²¹; P{TRiP.HMS00585}attP2

w¹¹¹⁸ P{GD5050}v13362

spn-A^JF01716

P{TRiP.JF01716}

y¹ v¹; P{TRiP.JF01716}attP2/TM3, Sb¹

y¹ sc^* v¹ sev²¹; P{TRiP.GL00669}attP2

y¹ v¹; P{TRiP.HMC03364}attP40

spn-A^HMJ21099

P{TRiP.HMJ21099}

y¹ v¹; P{TRiP.HMJ21099}attP40/CyO

Selected Drosophila classical alleles

Allele

Allele class

Mutagen

Publicly Available Stocks

okr^17-11

loss of function allele

ethyl methanesulfonate

okr^17-11 cn¹ bw¹/CyO

okr^AA

loss of function allele

ethyl methanesulfonate

okr^RU

ethyl methanesulfonate

okr^RU cn¹ bw¹/CyO, l(2)DTS513¹

okr^AG

loss of function allele

ethyl methanesulfonate

spn-A^093A

ethyl methanesulfonate

References (3)

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