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Analysis of a gene involved in multi...

Keeven, James Kevin.

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Analysis of a gene involved in multidrug resistance.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	Analysis of a gene involved in multidrug resistance./
Author:	Keeven, James Kevin.
Description:	63 p.
Notes:	Director: John E. Golin.
Contained By:	Dissertation Abstracts International62-12B.
Subject:	Biology, Genetics. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3037813
ISBN:	0493509151

Analysis of a gene involved in multidrug resistance.
Keeven, James Kevin.

Analysis of a gene involved in multidrug resistance. - 63 p.

Director: John E. Golin.

Thesis (Ph.D.)--The Catholic University of America, 2002.

Multiple drug resistance (MDR) occurs in many organisms including tumor cells that acquire resistance to different chemotherapeutic agents. The best characterized MDR locus in mammalian cells is the <italic>MDR1</italic> gene, encoding an integral membrane protein of the ATP-binding cassette (ABC) transporter family. <italic>MDR1</italic> uses the energy from ATP hydrolysis to pump substances out of the cell.

ISBN: 0493509151Subjects--Topical Terms:

1017730
Biology, Genetics.

Analysis of a gene involved in multidrug resistance.
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020 $a 0493509151
035 $a (UnM)AAI3037813
035 $a AAI3037813
040 $a UnM $c UnM
100 1 $a Keeven, James Kevin. $3 1250765
245 1 0 $a Analysis of a gene involved in multidrug resistance.
300 $a 63 p.
500 $a Director: John E. Golin.
500 $a Source: Dissertation Abstracts International, Volume: 62-12, Section: B, page: 5507.
502 $a Thesis (Ph.D.)--The Catholic University of America, 2002.
520 $a Multiple drug resistance (MDR) occurs in many organisms including tumor cells that acquire resistance to different chemotherapeutic agents. The best characterized MDR locus in mammalian cells is the <italic>MDR1</italic> gene, encoding an integral membrane protein of the ATP-binding cassette (ABC) transporter family. <italic>MDR1</italic> uses the energy from ATP hydrolysis to pump substances out of the cell.
520 $a <italic>Saccharomyces cerevisiae</italic> displays a phenotype analogous to mammalian multidrug resistance. As in mammalian cells, transporter proteins of the ABC family can pump out toxic substances. Members of this family include the Pdr5, Snq2 and Yor1 membrane proteins. Deletion of these genes renders cells hypersensitive to inhibitors, while overexpression leads to hyperresistance.
520 $a There is also a network of transcriptional regulators that control synthesis of these membrane proteins. Two activators, encoded by the <italic>PDR1</italic> and <italic>PDR3</italic> genes, bind to the promoters of these transporters to stimulate transcription.
520 $a Dominant gain-of-function mutations were previously isolated from a Pdr5 knockout multidrug sensitive strain that cause reversion to multidrug resistance. One of these mutations was shown to be in the <italic>YRR1</italic> gene which codes for a protein similar to the Pdr1 and Pdr3 transcription factors.
520 $a In this study, evidence is presented that all of the gain-of-function mutations are in the <italic>YRR1</italic> gene and that <italic>YRR1</italic> is identical to a previously identified locus: <italic>PDR2</italic>. Characterization of these <italic>PDR2</italic> alleles shows that acquired hyperresistance to drugs transported by the Sng2 and Yor1 proteins in these mutants is due solely to overproduction of these proteins in this gain-of-function background. This hyperresistance was shown to bypass any requirement for the Pdr1 and Pdr3 transcription factors. The target for resistance to drugs not transported by Sng2 or Yor1 such as cycloheximide was not found but a partial loss-of-function mutation that leads to cycloheximide sensitivity was shown to be in the <italic> UBP6</italic> gene, a ubiquitin protease. The <italic>PDR2</italic> gain-of-function mutations have no effect on <italic>UBP6</italic> transcription so any involvement of the <italic>UBP6</italic> gene in multidrug resistance is indirect.
590 $a School code: 0043.
650 4 $a Biology, Genetics. $3 1017730
690 $a 0369
710 2 0 $a The Catholic University of America. $3 1019220
773 0 $t Dissertation Abstracts International $g 62-12B.
790 $a 0043
790 1 0 $a Golin, John E., $e advisor
791 $a Ph.D.
792 $a 2002
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3037813