Homologous Recombination

Homologous Recombination requires

• Homologous sequences share high levels of sequence identity

• e. g. maternal and paternal copies of a chromosome

• e.g. sister chromatids after replication

• Antiparallel strands from homologous chromosomes can base-pair with one another

same order of genes nearly identical sequences slight differences due to replication errors, etc

this can happen anywhere there is homology (not just at ends)

Homologous Recombination is

an essential part of meiosis I

• Recombination that results in “crossing over” leads to diverse combinations of alleles in gametes

• This is one way that offspring are genetically different from their parents

• Connections between homologous pairs provide tension needed for meiosis to proceed

Homologous recombination requires

double- strand breaks

• Double-strand breaks are induced during meiosis I

• 5’ exonuclease creates an overhang

• The longer strand can base-pair with the homologouschromosome (Rad51-mediated)

diagram steps

1. paired homologous chromosomes

2. Spo11, Mre11 nuclease complex

3. one chromosome cut and ends processed

4. further processing of 5' ends by nuclease

5. RecA-like protein catalyzes strand exchange

6. dna synthesis

Both strands base pair with

strands from the homolog

• DNA Polymerase extends 3’ overhangs

• Ligase joins strands

• Four more single-strand cuts must be made so that the homologs can separate

• The pattern of cuts determines whether the HR results in a crossover or not

• Either way, the site of recombination has a region of heteroduplex

diagram 2 steps

1. capture of second strand

2. additional DNA synthesis

3. additional DNA synthesis followed by DNA ligation

4. double Holliday junction

5. DNA strands cut at arrows

6. chromosomes with or without crossover

   1. without crossover: arrows both pertical

   2. with: vertical left, horizontal right

Strand cutting and ligation

does not always occur at the site where new strand synthesis ends

These junctions can migrate

Mismatch repair can

fix any mismatches that arise in heteroduplex regions

• Mismatch repair proteins are active during meiosis

• Selection of the “correct” strand is random at each site of repair

• This can lead to over-representation of a given allele in the gamete population, but does not always because the reciprocal heteroduplex may be

repaired to favor the opposite allele

mismatch repair diagram

mismatch diagram text

heteroduplex generated during meiosis covers site where red and blue alleles differ

mismatch repair excises portion of blue strand

dna synthesis fills gap, creating an extra copy of the red allele