342
J . S E E D
double-stranded state from both normal and tumour cells is not
immediately usable as an efficient primer for D N A synthesis in vitro
(Bollum, 1959, 1960; Lehman, 1959; Keir, Binnie and Smellie, 1962).
The reaction apparently requires a single stranded (e.g. virus <£x 174
DNA) or heat-denatured D N A in order to proceed efficiently. Heating
is thought to separate the D N A strands (Doty, Marmur, Eigner and
Schildkraut, 1960). This result would of course be consistent with the
Watson-Crick replication hypothesis, where each D N A strand serves
as a template for the formation of its new complementary chain (see
p. 319).
The synthesis of R N A in vitro from the four triphosphates has been
demonstrated to occur with either a double or single stranded D N A
primer (Chamberlin and Berg, 1962; see also p. 320): in the cell types
considered here, it is clear from the experiments with actinomycin D
that R N A synthesis is dependent on the presence of D N A (see p. 329).
Moreover, from a study of R N A synthesis in vitro, Huang and Bonner
(1962) have shown that the DNA-protein complex in the chromatin
isolated from embryo-pea nuclei is not an efficient primer: in order
that appreciable R N A synthesis shall occur, the D N A must first be
divested of its associated his tone. Removal of the histone associated
with the D N A was found to increase fivefold the R N A synthesized, and
a reaction mixture containing the separated D N A was inactive when
an excess of histone was added. This result was thought to imply a role
for histone as a genetic "regulator" (Huang and Bonner, 1962).
It seems likely, therefore, that the D N A in a cell is not normally
accessible for the synthesis of either the D N A or the R N A for a new cell
and that certain processes, equivalent to changes in the physical state
of the deoxyribonucleo-protein (separation of strands and removal of
associated protein), have to take place in order to permit the accumulation of new DNA, R N A and, therefore, presumably protein for the
next mitosis (Seed, 1963b). Thus, the control of growth leading to the
replication of a normal cell may depend on a process which initiates the
unblocking of the D N A template*.
What then would be the nature ofthe loss of control in tumour-strain
cells, which is suggested by the dissociation in time of the onset of
nuclear R N A and protein synthesis from that of genetic material,
DNA? O n the scheme proposed here, these results would imply that
a large part of nuclear protein and R N A synthesis is not associated with
replication of the individual D N A strands as in normal cells, and that
some kind of permanent unblocking exists, permitting R N A and protein
but not D N A synthesis via the double stranded template of a tumour*For a discussion of evidence that a change of state of the D N A primer in bacteria is
associated with the action of certain inhibitors of DNA synthesis in vivo, see Billen (1962).
J . S E E D
double-stranded state from both normal and tumour cells is not
immediately usable as an efficient primer for D N A synthesis in vitro
(Bollum, 1959, 1960; Lehman, 1959; Keir, Binnie and Smellie, 1962).
The reaction apparently requires a single stranded (e.g. virus <£x 174
DNA) or heat-denatured D N A in order to proceed efficiently. Heating
is thought to separate the D N A strands (Doty, Marmur, Eigner and
Schildkraut, 1960). This result would of course be consistent with the
Watson-Crick replication hypothesis, where each D N A strand serves
as a template for the formation of its new complementary chain (see
p. 319).
The synthesis of R N A in vitro from the four triphosphates has been
demonstrated to occur with either a double or single stranded D N A
primer (Chamberlin and Berg, 1962; see also p. 320): in the cell types
considered here, it is clear from the experiments with actinomycin D
that R N A synthesis is dependent on the presence of D N A (see p. 329).
Moreover, from a study of R N A synthesis in vitro, Huang and Bonner
(1962) have shown that the DNA-protein complex in the chromatin
isolated from embryo-pea nuclei is not an efficient primer: in order
that appreciable R N A synthesis shall occur, the D N A must first be
divested of its associated his tone. Removal of the histone associated
with the D N A was found to increase fivefold the R N A synthesized, and
a reaction mixture containing the separated D N A was inactive when
an excess of histone was added. This result was thought to imply a role
for histone as a genetic "regulator" (Huang and Bonner, 1962).
It seems likely, therefore, that the D N A in a cell is not normally
accessible for the synthesis of either the D N A or the R N A for a new cell
and that certain processes, equivalent to changes in the physical state
of the deoxyribonucleo-protein (separation of strands and removal of
associated protein), have to take place in order to permit the accumulation of new DNA, R N A and, therefore, presumably protein for the
next mitosis (Seed, 1963b). Thus, the control of growth leading to the
replication of a normal cell may depend on a process which initiates the
unblocking of the D N A template*.
What then would be the nature ofthe loss of control in tumour-strain
cells, which is suggested by the dissociation in time of the onset of
nuclear R N A and protein synthesis from that of genetic material,
DNA? O n the scheme proposed here, these results would imply that
a large part of nuclear protein and R N A synthesis is not associated with
replication of the individual D N A strands as in normal cells, and that
some kind of permanent unblocking exists, permitting R N A and protein
but not D N A synthesis via the double stranded template of a tumour*For a discussion of evidence that a change of state of the D N A primer in bacteria is
associated with the action of certain inhibitors of DNA synthesis in vivo, see Billen (1962).