GEPHE SUMMARY
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Gephebase Gene
Entry Status
Published
GepheID
GP00001984
Main curator
Courtier
PHENOTYPIC CHANGE
Trait Category
Trait State in Taxon A
Drosophila melanogaster
Trait State in Taxon B
Drosophila melanogaster - more sensitive to camptothecin - no phenotypic effect with the camptothecin analog topotecan or with ionizing radiation
Ancestral State
Taxon A
Taxonomic Status
Taxon A
Latin Name
Common Name
fruit fly
Synonyms
Sophophora melanogaster; fruit fly; Drosophila melanogaster Meigen, 1830; Sophophora melanogaster (Meigen, 1830); Drosophila melangaster
Rank
species
Lineage
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Brachycera; Muscomorpha; Eremoneura; Cyclorrhapha; Schizophora; Acalyptratae; Ephydroidea; Drosophilidae; Drosophilinae; Drosophilini; Drosophila; Sophophora; melanogaster group; melanogaster subgroup
NCBI Taxonomy ID
is Taxon A an Infraspecies?
No
Taxon B
Latin Name
Common Name
fruit fly
Synonyms
Sophophora melanogaster; fruit fly; Drosophila melanogaster Meigen, 1830; Sophophora melanogaster (Meigen, 1830); Drosophila melangaster
Rank
species
Lineage
Show more ...
Brachycera; Muscomorpha; Eremoneura; Cyclorrhapha; Schizophora; Acalyptratae; Ephydroidea; Drosophilidae; Drosophilinae; Drosophilini; Drosophila; Sophophora; melanogaster group; melanogaster subgroup
NCBI Taxonomy ID
is Taxon B an Infraspecies?
No
GENOTYPIC CHANGE
Generic Gene Name
Cyp6g2
Synonyms
6g2; CG8859; Cyp6G2; Dmel\CG8859
String
Sequence Similarities
Belongs to the cytochrome P450 family.
GO - Molecular Function
GO:0020037 : heme binding
... show more
GO - Biological Process
GO:0046680 : response to DDT
... show more
GO - Cellular Component
UniProtKB
Drosophila melanogaster
Drosophila melanogaster
Presumptive Null
Molecular Type
Aberration Type
SNP Coding Change
Nonsynonymous
Molecular Details of the Mutation
N438T (A22652974C) and N439T (A22652978G) - exact causing mutation(s) not identified - semiquantitative RT-PCR revealed that this mutant produces little to no Cyp6d2 transcript. The mutation is thus also cis-regulatory.
Experimental Evidence
Taxon A | Taxon B | Position | |
---|---|---|---|
Codon | - | - | - |
Amino-acid | - | - | - |
Main Reference
Authors
Thomas AM; Hui C; South A; McVey M
Abstract
Many chemotherapeutic agents selectively target rapidly dividing cells, including cancer cells, by causing DNA damage that leads to genome instability and cell death. We used Drosophila melanogaster to study how mutations in key DNA repair genes affect an organism's response to chemotherapeutic drugs. In this study, we focused on camptothecin and its derivatives, topotecan and irinotecan, which are type I topoisomerase inhibitors that create DNA double-strand breaks in rapidly dividing cells. Here, we describe two polymorphisms in Drosophila Cyp6d2 that result in extreme sensitivity to camptothecin but not topotecan or irinotecan. We confirmed that the sensitivity was due to mutations in Cyp6d2 by rescuing the defect with a wild-type copy of Cyp6d2. In addition, we showed that combining a cyp6d2 mutation with mutations in Drosophila brca2 results in extreme sensitivity to camptothecin. Given the frequency of the Cyp6d2 polymorphisms in publcly available Drosophila stocks, our study demonstrates the need for caution when interpreting results from drug sensitivity screens in Drosophila and other model organisms. Furthermore, our findings illustrate how genetic background effects can be important when determining the efficacy of chemotherapeutic agents in various DNA repair mutants.
Additional References
RELATED GEPHE
Related Haplotypes
EXTERNAL LINKS
COMMENTS
This polymorphism is present in multiple lines - http://flybase.org/reports/FBal0282693
@Cis-RegulatoryInCodingRegion @ProbablyMultiNucleotideMutation
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