Essential Cell Biology 5th edition

214 CHAPTER 6 DNA Replication and Repair
Figure 6–22 Without a special mechanism to
replicate the ends of linear chromosomes,
DNA would be lost during each round
of cell division. DNA synthesis begins at
origins of replication and continues until
the replication machinery reaches the ends
of the chromosome. The leading strand is
synthesized in its entirety. But the ends of the
lagging strand can’t be completed, because
once the final RNA primer has been removed,
there is no mechanism for replacing it with
DNA. Complete replication of the lagging
strand requires a special mechanism to keep
the chromosome ends from shrinking with
each cell division.
lagging strand
5′
3′
RNA primers
5′
3′
leading strand
lagging strand
leading strand
lagging strand
3′
5′
3′
5′
REPLICATION FORK REACHES
END OF CHROMOSOME
RNA PRIMERS REPLACED BY DNA;
GAPS SEALED BY LIGASE
chromosome
end
leading strand
LAGGING STRAND
INCOMPLETELY REPLICATED
chromosomes and the double-strand DNA breaks that sometimes occur
accidentally in the middle ECB5 e6.21/6.22 of chromosomes. These breaks are dangerous
and must be immediately repaired, as we will see shortly.
Telomere Length Varies by Cell Type and with Age
In addition to attracting telomerase, the repetitive DNA sequences found
within telomeres attract other telomere-binding proteins that not only
physically protect chromosome ends, but help maintain telomere length.
Cells that divide at a rapid rate throughout the life of the organism—
those that line the gut or generate blood cells in the bone marrow, for
example—keep their telomerase fully active. Many other cell types, however,
gradually turn down their telomerase activity. After many rounds
Figure 6–23 Telomeres and telomerase
prevent linear eukaryotic chromosomes
from shortening with each cell division.
To complete the replication of the lagging
strand at the ends of a chromosome, the
template strand (orange) is first extended
beyond the DNA that is to be copied. To
achieve this, the enzyme telomerase adds to
the telomere repeat sequences at the 3ʹ end
of the template strand, which then allows
the newly synthesized lagging strand (red )
to be lengthened by DNA polymerase, as
shown. The telomerase enzyme itself carries
a short piece of RNA (blue) with a sequence
that is complementary to the DNA repeat
sequence; this RNA acts as the template for
telomere DNA synthesis. After the laggingstrand
replication is complete, a short
stretch of single-stranded DNA remains at
the ends of the chromosome; however, the
newly synthesized lagging strand, at this
point, contains all the information present
in the original DNA. To see telomerase in
action, view Movie 6.6.
TELOMERASE
BINDS TO
TEMPLATE STRAND
TELOMERASE ADDS
ADDITIONAL TELOMERE
REPEATS TO
TEMPLATE STRAND
COMPLETION OF LAGGING
STRAND BY DNA
POLYMERASE
telomere repeat sequences
3′
5′
5′
incomplete, newly synthesized lagging strand
3′
telomerase with its bound RNA template
5′ telomere repeat
3′ 5′
sequence
DNA
polymerase
3′ 5′
template of lagging strand
3′
extended template strand
3′
5′
direction of
telomere
DNA synthesis