TY - JOUR
T1 - Unstable DNA amplifications in methotrexate resistant Leishmania consist of extrachromosomal circles which relocalize during stabilization
AU - Beverley, Stephen M.
AU - Coderre, Jeffrey A.
AU - Santi, Daniel V.
AU - Schimke, Robert T.
N1 - Funding Information:
We thank the members of our laboratories for assistance and discussions. This work was supported by National Institutes of Health grants GM 14931 and CA 16318 (R. T. S.) and USPHS grant Al 19358 (D. V. S.). R. T. S. is an American Cancer Society Research Professor of Biology, and D. V. S. is a Burroughs Wellcome Scholar in Molecular Parasitology.
PY - 1984/9
Y1 - 1984/9
N2 - Methotrexate-resistant Leishmania tropical contain two separate regions of DNA amplification, one encoding the bifunctional thymidylate synthetase-dihydrofolate reductase (TS-DHFR) characteristic of protozoans and the other of yet unknown function. The amplified DNAs are initially found as extrachromosomal closed circular forms, which are unstable in the absence of selection. After prolonged culture in methotrexate the amplified DNAs are found as repetitive arrays associated with the chromosomal DNA fraction after CsCl-ethidium bromide density gradient centrifugation, and are stable once selection is removed. The molecular description of gene amplification in Leishmania thus closely parallels the cytological features of gene amplification in cultured mammalian cells.
AB - Methotrexate-resistant Leishmania tropical contain two separate regions of DNA amplification, one encoding the bifunctional thymidylate synthetase-dihydrofolate reductase (TS-DHFR) characteristic of protozoans and the other of yet unknown function. The amplified DNAs are initially found as extrachromosomal closed circular forms, which are unstable in the absence of selection. After prolonged culture in methotrexate the amplified DNAs are found as repetitive arrays associated with the chromosomal DNA fraction after CsCl-ethidium bromide density gradient centrifugation, and are stable once selection is removed. The molecular description of gene amplification in Leishmania thus closely parallels the cytological features of gene amplification in cultured mammalian cells.
UR - http://www.scopus.com/inward/record.url?scp=0021210054&partnerID=8YFLogxK
U2 - 10.1016/0092-8674(84)90498-7
DO - 10.1016/0092-8674(84)90498-7
M3 - Review article
C2 - 6467372
AN - SCOPUS:0021210054
SN - 0092-8674
VL - 38
SP - 431
EP - 439
JO - Cell
JF - Cell
IS - 2
ER -