Dr. Joshua Lederberg, President
The Rockefeller University

Dear Josh,
In answer to your Memo of April 8th, there are many indica’ “ons
that carcinogens preferentially damage DNA in the extended state, as
in the spacer regions between nucleosomes. Some of the evidence for
this is summarized briefly in a recent review (copy enclosed: pp. 523-
526). There is good evidence that the transcriptionally active regions
of chranatin in eukaryotic cells exist in an extended configuration,
and are therefore more prone to damage by alkylating carcinogens.
This is especially true for the ribosomal genes, in which the DNA is
nearly fully extended; the work of Fahmy and Fahmy (reprint enclosed)
shows the rDNA to be especially vulnerable to a variety of carcinogens.
There is some disagreanent among workers in the field on the changes in
distribution of DNA damage as a function of time after exposure to the
carcinogen, but many workers have observed the type of initial distri-
bution described, for example, by Jahn and Litman (reprint enclosed).
It gets more camplicated when one analyzes DNA repair processes and
must consider distributions of endonucleases, repair enzymes and poly-
. Ae 724 ADP-ribosylated proteins (which appear to act as signals for repair) in
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4 ae V different regions of the chromatin.

4 OBL

yy With warm regards,
f

Vincent G. ane Ray

Cre ee,

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