AREA CODE 608
PHONE 262-2177

McARDLE LABORATORY

FOR CANCER RESEARCH

MEDICAL CENTER UNIVERSITY OF WISCONSIN o MADISON, WISCONSIN 53706

September 30, 1371

Prof. Arthur Kornberg
Department of Biochemistry
Stanford University Medical Center
Palo A1 to, Cal ifornia 94304

Dear Arthur:

   Bob wells has shown me a preprint
and Kornberg on the involvement of RIlA
1413 DNA. In addition, Doug Brutlag to
Spring Harbor, and has now sent me his

of a paper by
polymerase in
d me about th
manuscript.

Brutlag, Shekman,
the replication of
s work at Cold

   I find this paper very exciting because it defines the involvement
of R!!A synthesis in DNA replication (initiation?) in a very clean way;
I expect that the study of the molecular basis of the coupling will proceed
well in this case. Also, I find the explicit statement of the possibility
of an RNA primer to be very constructive (;.e. testable). I am writing
because I think that the manuscript may not communicate information on the
generality of the phenomenon being described.

  In the introduction and discussion you present good reasons for
studyinq the possibility of an RNA primer; however, the average reader
may not be aware that the involvement of RNA synthesis in the initiation
of DNA replication has been studied extensively in A (mainly by us) and
has been suggested for E. - coli by Lark (1969 review).  In the case of A,
the evidence extends tothe point imp1 icating initiation rather than the
movement of replication forks. Further, it is found that the transcription
necessary for initiation must lie near the origin of replication. Finally
(as is now implicit in the classical experiment of Rene Thomas and
Elizabeth Bertani), the transcription which activates initiation of h
replication is subject to repression -- a fact which you can see has broad
biological import.

I enclose our published work on the A case so that you can evaluate

this point. As I stated at the outset, I find your manuscript to be a
valuable breakthrough in these studies, and in raising this point I do
not intend to detract from its value.

Sincerely,

William F. Dove

WFD/cw