Page 41 - Genetics_From_Genes_to_Genomes_6th_FULL_Part2

200 Chapter 6 DNA Structure, Replication, and Recombination

The unwinding of DNA beginning at the origin of rep- Figure 6.24 The bidirectional replication of a circular
lication produces two forks (Fig. 6.23a). As a result, repli- bacterial chromosome: An overview. (a) and (b) Replication
cation is generally bidirectional, with the replication forks proceeds in two directions from a single origin, creating two
moving in opposite directions as unwinding proceeds. At replication forks that move in opposite directions around the circle.
each fork, polymerase copies both template strands, one in Local unwinding of DNA at the replication forks creates supercoiled
twists in the DNA in front of the replication fork. (c) The action of
a continuous fashion, the other discontinuously as Okazaki topoisomerase enzymes helps reduce this supercoiling. (d) and
fragments (Fig. 6.23b). (e) When the two replication forks meet at the termination region,
In the circular E. coli chromosome, there is only one the entire chromosome has been copied. (f) Topoisomerase enzymes
origin of replication (Fig. 6.24a). When its two forks, mov- separate the two daughter chromosomes.
ing in opposite directions, meet at a designated termination (a) Original double helix Origin of replication
region about halfway around the circle from the origin of
replication, replication is complete (Figs. 6.24d–f).
Not surprisingly, local unwinding of the double helix
at a replication fork affects the chromosome as a whole. In Termination region
E. coli, the unwinding of a section of a covalently closed
circular chromosome overwinds and distorts the rest of the (b) Unwinding distorts molecule.
molecule (Fig. 6.24b). Overwinding reduces the number of
helical turns to less than the 1-every-10.5-nucleotides char- Newly Replication
acteristic of B-form DNA. The chromosome accommo- replicated forks
DNA
dates the strain of distortion by twisting back upon itself.
You can envision the effect by imagining a coiled tele- Overwound,
phone cord that overwinds and bunches up with use. The supercoiled Unreplicated DNA
additional twisting of the DNA molecule is called super- region
coiling. Movement of the replication fork causes more and
more supercoiling. (c) Topoisomerase relaxes supercoils by breaking, unwinding, and
This cumulative supercoiling, if left unchecked, would suturing the DNA.
wind the chromosome up so tightly that it would impede
the progress of the replication fork. A group of enzymes
known as DNA topoisomerases helps relax the supercoils
by nicking one or cutting both strands of the DNA—that is,
cleaving the sugar-phosphate backbone between two ad-
joining nucleotides (Fig. 6.24c). Just as a telephone cord 1. Topoisomerase 2. DNA cut by 3. Cut strands 4. Cut ends of
freed at the handset end can unwind and restore its normal in position to cut topoisom- rotate to strands rejoined
unwind
by ligase
DNA
erase
coiling pattern, the DNA strands, after cleavage, can rotate
relative to each other and thereby restore the normal coiling
density of one helical turn per 10.5 nucleotide pairs. The (d) Replication is bidirectional.
activity of topoisomerases thus allows replication to pro-
ceed through the entire chromosome by preventing super-
coils from accumulating in front of the replication fork. Termination region
Replication of a circular double helix sometimes produces
intertwined daughter molecules whose clean separation
also depends on topoisomerase activity (Fig. 6.24e and f). (e) Replication is complete when replication forks meet at the
In the much larger, linear chromosomes of eukaryotic termination region.
cells, bidirectional replication proceeds roughly as just
described but from many origins of replication. The mul- Termination region
tiple origins ensure that copying is completed within the
time allotted (that is, within the S period of the cell cycle).
In addition, because the lagging strand is synthesized as
Okazaki fragments, replication of the very ends of linear (f) Topoisomerases separate entwined daughter chromosomes,
chromosomes is also problematic. But eukaryotic chro- yielding two daughter molecules.
mosomes have evolved specialized termination structures
known as telomeres, which ensure the maintenance and
accurate replication of the two ends of each linear chro-
mosome. (Chapter 12 presents the details of eukaryotic
chromosome replication.)