October 6, 1963

Dr. A. ,Lwoff '
Ins titut Pasteur
?5, Rue du Docteur Roux
Paris, France

Dear Lwoff:

  Our evidence for thinking that the increase in DNA polymerase
activity induced by 'r2 phage infection is a protein distinct from pre-
existing coli polymerase is twofold. First, antiserum prepared against
polymerase purified from E. coli completely neutralizes this purified
polymerase as well as comparable amounts of activity in extracts of
normal cells.  It neutralizes il>% or less of the polymeraje activity in
extracts of r2 phage infected cells. Second, the augmented polymerase
activity of phage infected cells (about 93% of the total) requires the
addition of heat denatured DNA to the assay mixture in order for its
detection. By contrast, the polymerase activity in extracts of normal
E. coli shows little or no stimulation by the addition of such a primer.
Recently we have begun to fractionate the polymerase activity from
phage infected cells and there are indication6 that it behaves differently
from What we would expect of the polymerase activity in extracts of
normal cells.
and to look for a distinctive protein,  I doubt that it can be considered
proof of the existence of a distinctive protein.
izucleic acid and protein constituents in the phage infected cell react with
and modify the behavior of polymerase.

--

--

While this evidence has encouraged us to think there is

It is conceivable that

   I made these observations this summer and I am happy to have you
use them and interpret them in any way that you would like. Dr. H. V.
Aposhian, a postdoctoral fellow working under my direction, is pursuing
the purification of the phage induced polymerase and I will let you know if
we achieve any further clarification of the problem,

In a more speculative vein,  I have taken this evidence and that re-

ported by Bessman, formerly associated with our group(BBRC 1: 101,  1959),
on deoxyguanylate kinase to mean that there is, upon 'r2 infection, an abrupt
and complete immobilization of host DNA both with regard to its capacity
to serve as primer for future DNA replication and for information transfer
for new protein synthesis.  rhus in the case of the augmentation of levels
of pre-existing activities, as well as in the development of new enzyme
activities, totally new proteins are formed which may or may not resemble

-

Dr. A. Lwoff

- 2-

October 6, 1960

those previously produced in response to the host DNA.
that this kind of thinking is in keeping with ideas that you and Jacob have
developed independently from genetic lines of evidence.

I am guessing

With kindest regards,

Sincerely yours,

Arthur Kornberg

AK: e s