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Postdoc Position

Jim Mason masonj at niehs.nih.gov
Fri Jul 9 12:54:04 EST 1999

A postdoc position is available at the National Institute of
Environmental Health Sciences to study retrotransposition and telomere
structure in Drosophila. A strong background in the genetics and
molecular biology of Drosophila is preferred. Several ongoing projects
are described below. Inquiries should be directed to
masonj at niehs.nih.gov, or send an application with a CV and three letters
of recommendation to:

James Mason
Laboratory of Molecular Genetics
National Institute of Environmental Health Sciences
Research Triangle Park, NC 27709-2233
phone 919-541-4483
fax 919-541-7593

Drosophila maintains its telomere length by the targeted transposition
of two families of LINE-like retrotransposons, HeT-A and TART, although
HeT-A seems to predominate (Mason & Biessmann, Trends in Genet 11:
58-62, 1995). HeT-A is unique among retrotransposons, because it
performs a vital cellular function and because it does not encode a
reverse transcriptase (RT). Transposition seems to be controlled both by
the regulation of HeT-A transcription and by regulation of a RT of
unknown origin.

Unlike the extreme chromosome ends, the subterminal repeats in
Drosophila, also known as telomere associated sequences, TAS, are
similar to those found in other species (Pryde et al, Curr Opin Genet
Dev 7: 822-828, 1997). Reporter genes inserted into TAS sequences are
repressed and variegate, suggesting that TAS can act as a silencer and
nucleate a form of heterochromatin.

Five interrelated projects are currently underway in the lab. First, a
number of mutants have been identified that affect the frequency of
transposition. In order to maintain telomere length, transposition
should occur at a frequency of about 1%. We have confirmed this rate of
transposition (Biessmann et al, EMBO J 11: 4459-4469, 1992). A dominant
mutation has been identified on chromosome 2 that eliminates HeT-A
transposition. At the moment, nothing else is known about the mutant.
Two other mutants are known that increase transposition. One has not
been characterized. The other is a dominant mutation on chromosome 3
that increases the general activity of RT. This mutation also increases
HeT-A transposition 100X. These mutations need to be tested for their
effects on transposition of other structurally similar elements, such as
TART, jockey, F, G and I, and for effects on HeT-A transcription. They
also need to be mapped and characterized molecularly.

Second, HeT-A elements are being marked with either white with an
inverted intron, to measure transposition, or lacZ, to measure
transcription. These constructs will be used to examine steps in HeT-A
transposition. They can also be used to characterize the mutants
described above.

Third, mammalian L1 elements are similarly being marked with GFP with an
inverted intron to measure LINE transposition and its effects on genome
stability. It appears that, in the presence of certain mutant alleles of
p53, high levels of L-1 transposition induces apoptosis.

Fourth, analysis of mutants that have changed the expression of a white
reporter, P[wvar], in the 2L telomere indicate that terminal
deficiencies that remove some or all of the terminal HeT-A array
decrease the expression of the reporter, while new additions of HeT-A to
the 2L tip increase expression. This increased expression is modulated
by the condition of other telomeres in the cell, both homologous and
nonhomologous. Similarly, the expression of a mini-white reporter
inserted into various TAS regions is also affected by the condition of
other telomeres. Thus, a mini-white reporter in the 3R TAS increases
expression when the tip of 2L is deleted or has an insertion into TAS.
The nature of these interactions is under investigation.

Fifth, mutants that suppress the expression of a variegating white
reporter inserted in a TAS region have been isolated. These mutants are
analogous to the Su(var) mutants that suppress heterochromatic PEV,
although there is little if any overlap between the two sets of mutants.
The suppressors of telomeric position effect are currently being
characterized in terms of their effect on the expression of a number of
telomeric and other transgenic reporters. We hope that these new mutants
will identify proteins that are needed to establish or maintain telomere
chromatin structure.

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