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

HOMOLOGOUS RECOMBINATION
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DNA
MOVES
OUT
DNA MOVES IN
RuvB RuvA RuvB
DNA
MOVES
OUT
Figure 5–57 Enzyme-catalyzed branch
movement at a Holliday junction by
branch migration. In E. coli, a tetramer of
the RuvA protein (green) and two hexamers
of the RuvB protein (yellow) bind to the
open form of the junction. The RuvB
protein, which resembles the hexameric
helicases used in DNA replication (Figure
5–14), uses the energy of ATP hydrolysis
to spool DNA rapidly through the Holliday
junction, extending the heteroduplex region
as shown. The RuvA protein coordinates
this movement, threading the DNA strands
to avoid tangling. (PDB codes: 1IXR, 1C7Y.)
DNA MOVES IN
from the two Holliday junctions are thereby swapped, creating two chromosomes
that have crossed over.
How does the cell decide which Spo11-induced double-strand breaks to
resolve as crossovers? The answer is not yet known, but we know the decision
is an important one. The relatively few crossovers that do form are distributed
along chromosomes in such a way that a crossover in one position inhibits crossing-over
in neighboring regions. Termed crossover control, this fascinating but
poorly understood regulatory mechanism ensures the roughly even distribution
of crossover points along chromosomes. It also ensures that each chromosome—
no matter how small—undergoes at least one crossover every meiosis. For many
organisms, roughly two crossovers MBoC6 per m5.62/5.58 chromosome occur during each meiosis,
one on each arm. As discussed in detail in Chapter 17, these crossovers play an
important mechanical role in the proper segregation of chromosomes during
meiosis.
Whether a meiotic recombination event is resolved as a crossover or a
non-crossover, the recombination machinery leaves behind a heteroduplex region
where a strand with the DNA sequence of the paternal homolog is base-paired
with a strand from the maternal homolog (Figure 5–58). These heteroduplex
regions can tolerate a small percentage of mismatched base pairs, and because of
branch migration, they often extend for thousands of nucleotide pairs. The many
non-crossover events that occur in meiosis thereby produce scattered sites in the
germ cells where short DNA sequences from one homolog have been pasted into
the other homolog. Heteroduplex regions mark sites of potential gene conversion—where
the four haploid chromosomes produced by meiosis contain three
copies of a DNA sequence from one homolog and only one copy of this sequence
from the other homolog (see Figure 5–53), as explained next.
site of gene conversion
site of crossover
heteroduplex
heteroduplex
Figure 5–58 Heteroduplexes formed during meiosis. Heteroduplex DNA is present at sites
of recombination that are resolved either as crossovers or non-crossovers. Because the DNA
sequences of maternal and paternal chromosomes differ at many positions along their lengths,
heteroduplexes often contain a small number of base-pair mismatches.