Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

286 Chapter 5: DNA Replication, Repair, and Recombination
Figure 5–59 Gene conversion caused by mismatch correction. In
this process, heteroduplex DNA is formed at the sites of homologous
recombination between maternal and paternal chromosomes. If the maternal
and paternal DNA sequences are slightly different, the heteroduplex region
will include some mismatched base pairs, which may then be corrected
by the DNA mismatch repair machinery (see Figure 5–19). Such repair can
“erase” nucleotide sequences on either the paternal or the maternal strand.
The consequence of this mismatch repair is gene conversion, detected as
a deviation from the segregation of equal copies of maternal and paternal
alleles that normally occurs in meiosis.
heteroduplex generated during
meiosis covers site in gene
X where red and
blue alleles differ
MISMATCH REPAIR
EXCISES PORTION
OF BLUE STRAND
Homologous Recombination Often Results in Gene Conversion
In sexually reproducing organisms, it is a fundamental law of genetics that—aside
from mitochondrial DNA, which is inherited only through the mother—each
parent makes an equal genetic contribution to an offspring. One complete set of
nuclear genes is inherited from the father and one complete set is inherited from
the mother. Underlying this law is the accurate parceling out of chromosomes to
the germ cells (eggs and sperm) that takes place during meiosis. Thus, when a diploid
cell in a parent undergoes meiosis to produce four haploid germ cells, exactly
half of the genes distributed among these four cells should be maternal (genes
inherited from the mother of this parent) and the other half paternal (genes inherited
from the father of this parent). In some organisms (fungi, for example), it is
possible to recover and analyze all four of the haploid gametes produced from a
single cell by meiosis. Studies in such organisms have revealed rare cases in which
the parceling out of genes violates the standard genetic rules. Occasionally, for
example, meiosis yields three copies of the maternal version of a gene and only
one copy of the paternal allele. Alternative versions of the same gene are called
alleles, and it is the divergence from their expected distribution during meiosis
that is known as gene conversion. Genetic studies show that only small sections
of DNA typically undergo gene conversion, and in many cases only a part of a
gene is changed.
Several pathways in the cell can lead to gene conversion, but one of the most
important arises from a particular consequence of recombination during meiosis.
We have seen that both crossovers and non-crossovers produce heteroduplex
regions of DNA. If the two strands that make up a heteroduplex region do not have
identical nucleotide sequences, mismatched base pairs are formed, and these are
often repaired by the cell’s mismatch repair system (see Figure 5–19). However, the
mismatch repair system cannot distinguish between the paternal and maternal
strands and will randomly choose the strand to be used as a template. As a consequence,
one allele will be lost and the other duplicated (Figure 5–59), resulting
in net “conversion” of one allele to the other. Thus, gene conversion, originally
regarded as a mysterious deviation from the rules of genetics, can be seen as a
straightforward consequence of the mechanisms of homologous recombination.
DNA SYNTHESIS
FILLS GAP, CREATING
AN EXTRA COPY OF
THE RED ALLELE OF
GENE X
gene X
MBoC6 m5.66/5.60
Summary
Homologous recombination describes a flexible set of reactions resulting in the
exchange of DNA sequences between a pair of identical or nearly identical duplex
DNA molecules. In all cells, this process is essential for the error-free repair of chromosome
damage, particularly double-strand breaks and broken or stalled replication
forks. Homologous recombination is also responsible for the crossing-over of
chromosomes that occurs during meiosis. Homologous recombination takes place
through a variety of pathways, but they have in common a strand-exchange step
whereby a single strand from one DNA duplex invades a second duplex and basepairs
with one strand while displacing the other. This reaction, catalyzed by the
RecA/Rad51 family of proteins, can only occur if the invading strand can form a
short stretch of consecutive nucleotide pairs with one of the strands of the duplex.
This requirement ensures that homologous recombination occurs only between
identical or very similar DNA sequences.