In their work with DNA polymerase, Kornberg and his colleagues had found that it could induce a seemingly spontaneous synthesis
of an adenine-thymine polymer, without a template. This phenomenon raised a number of questions about the nature of chemical
bonds in nucleotides and nucleic acids, and the exact mechanism of the polymerase. In this letter, Kornberg responded to Henry
Sobell's research proposal on this topic.
Number of Image Pages:
1 (79,633 Bytes)
1965-04-22 (April 22, 1965)
Sobell, Henry M.
Massachusetts Institute of Technology
Original Repository: Stanford University Libraries. Department of Special Collections and University Archives. Arthur Kornberg Papers
Reproduced with permission of Arthur Kornberg.
Medical Subject Headings (MeSH):
"Creating Life in the Test Tube," 1959-1970
Letter from Henry M. Sobell to Arthur Kornberg (December 31, 1964)
April 22, 1965
You were very kind to send me a copy of your research proposal and ideas on purine-pyrimidine base pairs as you saw them from
a crystallographic vantage point. On a couple of occasions I wanted to respond but preferred to wait until I could make a
more meaningful comment. I think now that I had better acknowledge your thoughtfulness in sending this proposal before you
think me impolite or indifferent.
From all the work that we have done with enzymatic replication and from everything that we have been told about the man's
job that the boy's hydrogen bonding is reputed to be doing, we are inclined to give the polymerase a specia1 role. This
role would be the recognition of a base pair, and the subsequent diester bond formation to the chain end would depend upon
the proper steric conformation of the complex that comes with the recognition of the enzyme of this base pair. Whether this
base pair has the Hoogsteen or the W-C configuration we of course have no way of knowing. We have been struck by the facility
with which dAT primes the polymerase but we have attributed this to the ready breathing of the helical template. I am inclined
to feel that the initiation of a de novo reaction comes from an enzymatic synthesis of oligomers; we have a dogmatic reluctance
to invoke any non-enzymatic events, and this carries over to a reaction as bizarre as the in vitro development of dAT.
I hope you won't feel inhibited about speculating and working on the nature of copolymer and homopolymer syntheses and
replications because of any fund of knowledge residing with those of us who have been working on this problem. It simply
is too fragmentary and shallow to inhibit you from making major contributions to this area. I will be very eager to hear
how things are going with you.