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July 01, 1994 - Image 35

Resource type:
Text
Publication:
The Detroit Jewish News, 1994-07-01

Disclaimer: Computer generated plain text may have errors. Read more about this.



Repair Enzymes
Produce Mutations

Vital "repair enzymes" responsi-
ble for preventing genetic muta-
tions are at times hoodwinked
into causing such mutations
themselves, according to a Weiz-
mann Institute study, which ap-
peared in the Journal of
Biological Chemistry.
It is well recognized that envi-
ronmental stress factors such as
ultraviolet light or certain chem-
icals may create lesions on DNA
strands, preventing the DNA
molecule from issuing clear in-
structions on how to form an
identical replica of itself. Were it
not for the "rescue" operations of
special "repair enzymes" — pro-
teins that search for lesions, cut
them away and replace them
with healthy DNA material —
mutations would be formed in un-
controllable fashion and life on
earth would become nearly im-
possible. However, Professor Zvi
Livneh and doctoral student
Orna Cohen-Fix of the Institute's
Department of Biochemistry
have now found that these same
enzymes can be duped into pro-
ducing the very mutations that
they set out to avert.
"Our hypothesis," Professor
Livneh says, "is that this occurs
when two different lesions face
one another on complementary
DNA strands." Initially, the
restoration process proceeds nor-
mally, with the repair enzyme ex-
cising one of the lesions. But then,
says Professor Livneh, "the en-
zyme encounters an unexpected
situation. The reserve store of in-
formation on the opposite strand,
which it requires in order to fill
in the gap, turns out to be faulty
as well. But the point of no return
has been reached in the process,
and the enzymatic machinery is
left with no choice other than to
go on and duplicate the defective
material — thereby producing a
mutation."
This newly discovered process
appears to be an "alternative"
mutation pathway; in the more
commonly recognized pathway,
ordinarily dormant proteins
called bypass factors help the
DNA copying machinery to cir-
cumvent lesions. While these by-
pass factors enable the
duplication process to proceed,
and thus keep the cell alive, an
almost inevitable result of their
activity is permanent mutation
in the cell's genetic material.
Professor Livneh and Ms. Co-
hen-Fix used an original model
system in which ultraviolet-light-
induced genetic changes are pro-
duced in test-tube experiments
using a protein extract from the
bacterium Esherichia coli. Adap-
tation of this system to ultravio-
let-light-exposed mammalian cell
cultures will allow the investiga-
tion of such dual pathways in
mammalian systems.

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