STANFORD UNIVERSITY
MEDICAL CENTER
PALO ALTO, CALIFORNIA

DEPARTMENT OF GENETICS
School of Medicine

December 8, 1959

Dear Art--

When you get back:
Have you thought what are the possible substrates of the"unwinding enzyme"?

I could visualize that UE might bind itself to one site of the primer DNA;
unless this were immediately followed by the p@lymerase, this would not be
very effective. I can't conceive of one (or a few) molecules of UE literally
unwinding the DNA, and holding it so. As a third alternative, I would suggest
that there is some other Substrate for the UE, whose functien is to form
relatively easily dissociated complexes between UES and the DNA sites, thereby
breaking the hydrogen bonds between complementary bases. These cemplaxes, in
turn, would be displaced by the polymerase action.

What could X be? I¢ might be the deoxyside triphosphates themselves -- in
effect this is what you are assaying for now. I wonder if it might not be the
ribosides or their phopshates. Alternatively, there might be some quite dif-
ferent bonding, perhaps comparable to, but weaker than, the formaldehyde com-
plexes with the amino groups.

The main point of the remark is that it might be futile to look for the
UE effect as an accessory to polymerase action in highly purified preps., the
soluble components, other than the deoxyphosphates, might be critical too.

- pon Joshua
vf
pr al?