Essential Cell Biology 5th edition

DNA Repair
219
TOP STRAND
REPLICATED
CORRECTLY
original parent strand
C
5′
3′
parent DNA
molecule
C
G
3′ DNA
REPLICATION
5′
MISTAKE
OCCURS DURING
REPLICATION OF
BOTTOM STRAND
G
new strand
new strand with error
A
REPLICATION
WITHOUT
REPAIR
strand with error
A
T
newly synthesized
strand
DNA WITH
PERMANENT
MUTATION
G
original parent strand
newly synthesized
strand
C
G
DNA WITH
ORIGINAL
SEQUENCE
repair gene are unaffected until the undamaged copy of the same gene
is randomly mutated in a somatic cell. This mutant cell—and all of its
progeny—are then deficient in mismatch repair; they therefore accumulate
mutations more rapidly than do normal cells. Because cancers arise
from cells that have accumulated multiple mutations, a cell deficient in
mismatch repair has a greatly enhanced chance of becoming cancerous.
Thus, inheriting a single damaged mismatch repair gene strongly predisposes
an individual to cancer.
original parent strand
Figure 6–28 Errors made during DNA
replication must be corrected to avoid
mutations. If uncorrected, a mismatch will
lead to a permanent mutation in one of the
two DNA molecules produced during the
next round of DNA replication.
Double-Strand DNA Breaks Require a Different Strategy
for Repair
ECB5 e6.27/6.28
The repair mechanisms we have discussed thus far rely on the genetic
redundancy built into every DNA double helix. If nucleotides on one
strand are damaged, they can be repaired using the information present
in the complementary strand. This feature makes the DNA double helix
especially well-suited for stably carrying genetic information from one
generation to the next.
But what happens when both strands of the double helix are damaged
at the same time? Mishaps at the replication fork, radiation, and various
chemical assaults can all fracture DNA, creating a double-strand break.
Such lesions are particularly dangerous, because they can lead to the
fragmentation of chromosomes and the subsequent loss of genes.
TOP STRAND
REPLICATED
CORRECTLY
original parent strand
C
5′
parent DNA
molecule
C
3′ DNA
REPLICATION
new strand
G
3′
G
5′
MISTAKE
OCCURS DURING
REPLICATION OF
BOTTOM STRAND
new strand with error
A
G
MISMATCH
REPAIR
C
G
ORIGINAL
SEQUENCE
RESTORED
original parent strand
Figure 6–29 Mismatch repair eliminates replication errors and restores the original DNA sequence. When mistakes occur
during DNA replication, the repair machinery must replace the incorrect nucleotide on the newly synthesized strand, using the original
parent strand as its template. This mechanism eliminates the error, and allows the original sequence to be copied during subsequent
rounds of replication.