The objective of these studies is to provide information about changes in the ribosomal genes that occur under magnifying conditions in Drosophila. The proposed experiments concern 1) the mechanism of magnification and 2) the nature and regulation of gene products that mediate the process of magnification. The mechanism of magnification will be examined using genetic, cytological and molecular experiments that will provide information concerning the meiotic and premeiotic nature of the magnifying events, their sequence and site specificity and the role of the GO rDNA amplification in magnification. We will also map the region of the Y chromosome that induces magnifying events in females and examine the basis for the instability of the magnified products. Gene products that mediate the process of magnification will include chromosomal proteins involved in pairing of sister strands and recombinase(s). We have begun studies on a mutation, claret constitutive magnifier (ca-cm), that results in instability at bb under nonmagnifying conditions. Genetic evidence suggests that ca-cm results in unequal sister strand pairing at bb. We propose to clone and characterize the wild-type and mutant genes in order to identify the function of the wild-type gene product and the nature of the change in the mutant allele. A second class of mutation, the Ring magnifier (Rm) mutations, results in magnification of bb in ring chromosomes; these alleles do not magnify in the absence of Rm. We will carry out P element, EMS and X-ray mutagenesis screens to revert these dominant mutations. The revertants will provide information regarding the nature of the Rm mutations and will allow us to clone the wild-type and mutant genes in order to identify the function of the wild-type gene product. A plus/minus molecular screen for DNA sequences encoding other products involved in the magnifying process will be carried out and experiments determine the function and regulation of these products will be initiated. These studies will increase our knowledge of the processes which result in increased or reduced ribosomal gene number under magnifying conditions; they will contribute to our understanding of gene copy number regulation in higher organisms.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM031279-06
Application #
3279232
Study Section
Genetics Study Section (GEN)
Project Start
1983-07-01
Project End
1991-06-30
Budget Start
1988-07-01
Budget End
1989-06-30
Support Year
6
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Duke University
Department
Type
Schools of Medicine
DUNS #
071723621
City
Durham
State
NC
Country
United States
Zip Code
27705
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Endow, S A (1991) The emerging kinesin family of microtubule motor proteins. Trends Biochem Sci 16:221-5
Endow, S A; Hatsumi, M (1991) A multimember kinesin gene family in Drosophila. Proc Natl Acad Sci U S A 88:4424-7
Komma, D J; Graves, H; Endow, S A (1989) Mutant alleles of the meiotic locus, mei-9, differ in degree of effects on rod chromosome magnification and ring chromosome transmission in Drosophila. Genet Res 53:155-61
Endow, S A; Atwood, K C (1988) Magnification: gene amplification by an inducible system of sister chromatid exchange. Trends Genet 4:348-51
Komma, D J; Endow, S A (1987) Incomplete Y chromosomes promote magnification in male and female Drosophila. Proc Natl Acad Sci U S A 84:2382-6
Endow, S A; Komma, D J (1986) One-step and stepwise magnification of a bobbed lethal chromosome in Drosophila melanogaster. Genetics 114:511-23
Komma, D J; Endow, S A (1986) Magnification of the ribosomal genes in female Drosophila melanogaster. Genetics 114:859-74