1 0 . D N A A N D R N A S Y N T H E S I S
343
strain cell (that there is also present in a HeLa cell an R N A component
still associated with D N A synthesis is indicated by the correlation of a
part of the cytidine uptake into R N A with cytidine uptake into D N A as
found in autoradiographic studies on HeLa cells (Seed, 1963a)). One
plausible manner of unblocking would clearly be the deletion or mismatching of a growth-controlling protein. I have already pointed out
that this situation could enable D N A synthesis to be initiated automatically at a point in interphase, when certain necessary prior
syntheses, possibly enabling conversion of the D N A into the priming
state for D N A synthesis, had occurred via the unblocked portion of the
double-stranded template (Seed, 1961, 1963b). In this connexion it is
of interest that, from a study of the action of u.v. light and puromycin
(a specific inhibitor of protein synthesis) on L-strain cells, Powell
(1962) has reported that a preliminary protein synthesis is necessary
for the initiation of D N A synthesis in these cells.
It is noteworthy that in rapidly growing bacterial cultures (e.g.
E. coli), the syntheses of DNA, R N A and protein appear to be largely
dissociated (Barner and Cohen, 1958; McFall and Magasanik, 1962)
and also that in E. coli, the D N A apparently has no histone in association with it (Wilkins and Zubay, 1959).
One probable consequence of a physical abnormality upsetting the
balance of the syntheses (DNA, R N A and protein) in a self-replicating
composite structure, such as a chromosome, is that there would be
mechanical difficulties (perhaps analogous to the separation of an imperfect zip) when the two imperfect halves attempted to separate after
completion of the replication cycle, that is in metaphase. It is well
known that the frequency of metaphases, relative to the other stages
of mitosis, is higher in tumours than in dividing normal tissues, indicating that tumour cells spend longer in metaphase. It is also of interest
that aneuploidy and the frequency of chromosome fragments and
abnormalities are higher in tumours than in dividing normal cells
(e.g. Koller 1947; Timonen and Therman, 1950). The longer duration
of metaphase in HeLa cells, as compared with normal embryonic cells
has been observed in culture (Seed, unpublished).
Evidence concerning the onset of synthesis in rapidly dividing cells
also comes from radiation studies (Seed, 1961). In experiments with
cells freshly prepared from normal tissues it appears that inhibition of
the onset of D N A synthesis is observed after radiation during the presynthetic period with doses of a few hundred r. However, similar
experiments with cells derived from, or capable of producing, tumours
have failed to show this inhibition of D N A synthesis by irradiation
in the pre-synthetic period (Howard and Pelc, 1953; Pelc and Howard,
1955; Holmes and Mee, 1954; Kelly, Hirsch, Beach and Payne, 1955;
343
strain cell (that there is also present in a HeLa cell an R N A component
still associated with D N A synthesis is indicated by the correlation of a
part of the cytidine uptake into R N A with cytidine uptake into D N A as
found in autoradiographic studies on HeLa cells (Seed, 1963a)). One
plausible manner of unblocking would clearly be the deletion or mismatching of a growth-controlling protein. I have already pointed out
that this situation could enable D N A synthesis to be initiated automatically at a point in interphase, when certain necessary prior
syntheses, possibly enabling conversion of the D N A into the priming
state for D N A synthesis, had occurred via the unblocked portion of the
double-stranded template (Seed, 1961, 1963b). In this connexion it is
of interest that, from a study of the action of u.v. light and puromycin
(a specific inhibitor of protein synthesis) on L-strain cells, Powell
(1962) has reported that a preliminary protein synthesis is necessary
for the initiation of D N A synthesis in these cells.
It is noteworthy that in rapidly growing bacterial cultures (e.g.
E. coli), the syntheses of DNA, R N A and protein appear to be largely
dissociated (Barner and Cohen, 1958; McFall and Magasanik, 1962)
and also that in E. coli, the D N A apparently has no histone in association with it (Wilkins and Zubay, 1959).
One probable consequence of a physical abnormality upsetting the
balance of the syntheses (DNA, R N A and protein) in a self-replicating
composite structure, such as a chromosome, is that there would be
mechanical difficulties (perhaps analogous to the separation of an imperfect zip) when the two imperfect halves attempted to separate after
completion of the replication cycle, that is in metaphase. It is well
known that the frequency of metaphases, relative to the other stages
of mitosis, is higher in tumours than in dividing normal tissues, indicating that tumour cells spend longer in metaphase. It is also of interest
that aneuploidy and the frequency of chromosome fragments and
abnormalities are higher in tumours than in dividing normal cells
(e.g. Koller 1947; Timonen and Therman, 1950). The longer duration
of metaphase in HeLa cells, as compared with normal embryonic cells
has been observed in culture (Seed, unpublished).
Evidence concerning the onset of synthesis in rapidly dividing cells
also comes from radiation studies (Seed, 1961). In experiments with
cells freshly prepared from normal tissues it appears that inhibition of
the onset of D N A synthesis is observed after radiation during the presynthetic period with doses of a few hundred r. However, similar
experiments with cells derived from, or capable of producing, tumours
have failed to show this inhibition of D N A synthesis by irradiation
in the pre-synthetic period (Howard and Pelc, 1953; Pelc and Howard,
1955; Holmes and Mee, 1954; Kelly, Hirsch, Beach and Payne, 1955;