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PMID: 1672636 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Direct and inverted DNA repeats associated with P-glycoprotein gene amplification in drug resistant Leishmania.

The EMBO journal ·Vol. 10 ·No. 4 ·1991-04-00 ·Pages 1009-16

Ouellette M, Hettema E, Wüst D, Fase-Fowler F, Borst P

Abstract

The H circle of Leishmania species contains a 30 kb inverted duplication separated by two unique DNA segments, a and b. The corresponding H region of chromosomal DNA has only one copy of the duplicated DNA. We show here that the chromosomal segments a and b are flanked by inverted repeats (198 and 1241 bp) and we discuss how these repeats could lead to formation of H circles from chromosomal DNA. Selection of Leishmania tarentolae for methotrexate resistance indeed resulted in the de novo formation of circles with long inverted duplication, but two mutants selected for arsenite resistance contained new H region plasmids without such duplications. One of these plasmids appears due to a homologous recombination between two P-glycoprotein genes with a high degree of sequence homology. Our results show how the same DNA region in Leishmania may be amplified to give plasmids with or without long inverted duplications and apparently by different mechanisms.

MeSH Terms
ATP Binding Cassette Transporter, Subfamily B, Member 1 Animals Base Sequence Cell Line Cloning, Molecular DNA DNA, Circular/genetics DNA, Protozoan/genetics Drug Resistance/genetics Gene Amplification Leishmania/drug effects,genetics Membrane Glycoproteins/genetics Methotrexate/pharmacology Molecular Sequence Data Repetitive Sequences, Nucleic Acid
Chemicals
ATP Binding Cassette Transporter, Subfamily B, Member 1 DNA, Circular DNA, Protozoan Membrane Glycoproteins DNA Methotrexate
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Ouellette M
Division of Molecular Biology, Netherlands Cancer Institute, Amsterdam.
Hettema E
Wüst D
Fase-Fowler F
Borst P
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1991-04-00
Pages
1009-16
Language
English
Region
England
NLM ID
8208664
PMCID
PMC452745
Subset
IM
Databases
GENBANK
M55397, M55398, M55399, M55400, M55401, M55402
External Links
PubMed source PMC Full Text View journal details
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