Worm Breeder's Gazette 13(5): 22 (February 1, 1995)

These abstracts should not be cited in bibliographies. Material contained herein should be treated as personal communication and should be cited as such only with the consent of the author.

Suppressors of let-60 Dominant Negative Mutations.

Trent Gu, Min Han

Department of MCD Biology, University of Colorado, Boulder

The gene let-60 ras plays a key role in a genetic pathway
that specifies the vulva cell fate. Loss of function (lf)
mutations of let-60 cause Vul (and therefore is egg laying
defective), in which all of the VPCs take on the hyperdermal
cell fate. Hyperactive mutations or gain of function (gf)
of let-60 cause Muv, in which more than three VPCs are differentiated
to become vulva cells. Ras is used to transmit cell growth
signals in many organisms from yeast to human. Studying
the role of let-60 ras pathway in C. elegans will help in
understanding the Ras signal transduction pathway in
other organisms.
How the lef-60 ras pathway is negatively controlled is
not well understood. For example, we don't know how the
kinases downstream of let-60 ras are kept inactive. To
isolate the negative regulators downstream of let-60
ras, we have screened and isolated suppressors that revert
the Vul phenotype caused by a let-60 ras dominant-negative
(dn) mutation. Seven different genes are identified from
fourteen recessive extragenic suppressors.
The preliminary mapping and complementation results
of nine recessive extragenic suppressors are shown below
The suppression of let-60 (dn) by ku105 is not allele specific
since ku105 can suppress three different let-60 (dn) alleles:
sy94, syl01,and syl00. ku105 homozygous suppress let-60(dn)
better than ku105/Df, indicating that ku105 is possibly
a recessive antimorph.
Since previous genetic study suggests that the let-60
ras (dn) mutation decreases the pathway's activity (thus
leading to the vulvaless phenotype), potential suppressors
are expected to increase or restore the normal activity
of the pathway.