Essential Cell Biology 5th edition

DNA Replication
209
(A)
ACTUAL 5′-to-3′ STRAND GROWTH
5′ 3′
end of growing
P P P
DNA strand
(B) HYPOTHETICAL 3′-to-5′ STRAND GROWTH
5′
3′
end of growing
P P P P P
DNA strand
HYDROLYSIS OF INCOMING
DEOXYRIBONUCLEOSIDE
TRIPHOSPHATE PROVIDES
ENERGY FOR
POLYMERIZATION
5′ 3′ 5′ 3′
P P P
P P P
P
P
incorrect
deoxyribonucleoside
triphosphate
incorrect
deoxyribonucleoside
triphosphate
P
P
HYDROLYSIS OF PHOSPHATE
BOND AT 5′ END OF GROWING
STRAND PROVIDES ENERGY
FOR POLYMERIZATION
5′ 3′
P P P P
P
P
5′
P
P P P
3′
PROOFREADING
PROOFREADING
P
P
P
P
HYDROLYSIS OF INCOMING
DEOXYRIBONUCLEOSIDE
TRIPHOSPHATE PROVIDES
ENERGY FOR
POLYMERIZATION
5′ 3′
P P P
5′ 3′
P P P P
HIGH-ENERGY BOND IS
CLEAVED, PROVIDING THE
ENERGY FOR POLYMERIZATION
P
P
P
P
P
3′ end produced when
incorrect nucleotide
is removed by
proofreading
correct
deoxyribonucleoside
triphosphate
5′ end produced
when incorrect
nucleotide is
removed by
proofreading
P
P
P
correct
deoxyribonucleoside
triphosphate
P
P
P
5′
P P P
5′
P P P
3′
FURTHER POLYMERIZATION
IS BLOCKED
3′
POLYMERIZATION CANNOT
PROCEED, AS NO HIGH-ENERGY
BOND IS AVAILABLE TO DRIVE
THE REACTION
Figure 6−16 For proofreading to take place, DNA polymerization must proceed in the 5ʹ-to-3ʹ direction.
(A) Polymerization in the normal 5ʹ-to-3ʹ direction allows the DNA strand to continue to be elongated after an
incorrectly added nucleotide (gray) has been removed by proofreading (see Figure 6−14). (B) If DNA synthesis
instead proceeded in the backward 3ʹ-to-5ʹ direction, the energy for polymerization would come from the hydrolysis
of the phosphate groups at the 5ʹ end of the growing chain (orange), rather than the 5ʹ end of the incoming
nucleoside triphosphate. Removal of an incorrect nucleotide would block the addition of the correct nucleotide
(red ), as there are no high-energy phosphodiester bonds remaining at the 5ʹ end of the growing strand.
ECB5 eQ6.16-6.16
Primase is an example of an RNA polymerase, an enzyme that synthesizes
RNA using DNA as a template. A strand of RNA is very similar chemically
to a single strand of DNA except that it is made of ribonucleotide
subunits, in which the sugar is ribose, not deoxyribose; RNA also differs
from DNA in that it contains the base uracil (U) instead of thymine (T)
(see Panel 2–7, pp. 78–79). However, because U can form a base pair with
A, the RNA primer is synthesized on the DNA strand by complementary
base-pairing in exactly the same way as is DNA.
For the leading strand, an RNA primer is needed only to start replication
at a replication origin; at that point, the DNA polymerase simply takes
over, extending this primer with DNA synthesized in the 5ʹ-to-3ʹ direction.
But on the lagging strand, where DNA synthesis is discontinuous,
new primers are continuously needed to keep polymerization going (see
Figure 6–13). The movement of the replication fork continually exposes
unpaired bases on the lagging-strand template, and new RNA primers
must be laid down at intervals along the newly exposed, single-stranded