Essential Cell Biology 5th edition

DNA Repair
221
the repair, a recombination-specific nuclease chews back the 5ʹ ends of
the two broken strands at the break (Figure 6–31B). Then, with the help
of specialized enzymes (called recA in bacteria and Rad52 in eukaryotes),
one of the broken 3ʹ ends “invades” the unbroken homologous
DNA duplex and searches for a complementary sequence through basepairing
(Figure 6–31C). Once an extensive, accurate match is made, the
invading strand is elongated by a repair DNA polymerase, using the complementary
undamaged strand as a template (Figure 6–31D). After the
repair polymerase has passed the point where the break occurred, the
newly elongated strand rejoins its original partner, forming base pairs
that hold the two strands of the broken double helix together (Figure
6–31E). Repair is then completed by additional DNA synthesis at the 3ʹ
ends of both strands of the broken double helix (Figure 6–31F), followed
by DNA ligation (Figure 6–31G). The net result is two intact DNA helices,
for which the genetic information from one was used as a template to
repair the other.
Homologous recombination can also be used to repair many other types
of DNA damage, making it perhaps the most handy DNA repair mechanism
available to the cell: all that is needed is an intact homologous
(A)
5′
3′
3′
5′
(B)
5′
3′
3′
5′
(C)
5′
3′
double-strand break
5′
5′
NUCLEASE DIGESTS 5′ ENDS
OF BROKEN STRANDS
3′
3′
5′
3′
5′
5′
3′
3′
5′
5′
3′
STRAND INVASION BY
COMPLEMENTARY BASE-PAIRING
3′
5′
replicated DNA
molecules
3′
5′
(D)
5′
3′
5′
REPAIR POLYMERASE SYNTHESIZES DNA (GREEN)
USING UNDAMAGED COMPLEMENTARY DNA AS A TEMPLATE
3′
5′
3′
5′
(E)
5′
3′
3′
5′
(F)
5′
3′
3′
5′
(G)
5′
3′
3′
5′
5′
INVADING STRAND RELEASED; COMPLEMENTARY
BASE-PAIRING ALLOWS BROKEN HELIX TO RE-FORM
DNA SYNTHESIS CONTINUES USING COMPLEMENTARY STRANDS
FROM DAMAGED DNA AS A TEMPLATE
DNA LIGATION
5′
DOUBLE-STRAND BREAK IS
ACCURATELY REPAIRED
Figure 6–31 Homologous recombination
flawlessly repairs DNA double-strand
breaks. This is the preferred method for
repairing double-strand breaks that arise
shortly after the DNA has been replicated
but before the cell has divided. See
text for details. (Adapted from M. McVey
et al., Proc. Natl. Acad. Sci. U.S.A. 101:
15694–15699, 2004.)