Homologous Recombination

1
Homologous Recombination

• Exchange between pair of homologous DNA segments
• Genetic exchange during meiosis
• DNA repair

2
Strand Invasion

• Base pairing between complementary strands of two
  different duplexes
• Heteroduplex

3
RecA Protein Catalyzes Strand Invasion

• Associates invading strand with DNA duplex being
  invaded
• Transient three-stranded structure
• Heteroduplex formation

4
Double Strand Break Repair

• Associated sister chromatids
• Strand invasion by broken chromosome
• DNA synthesis using unbroken chromosome as
  template

5
Meiotic Recombination

• Double-strand break
• Strand invasion
• Holliday junction
• Resolution either regenerates original duplexes
  or generates crossover

6
Holliday Junction

• Isomerization
• Resolution by cutting strands

7
Gene Conversion

• Divergence in allele distribution
• Occurs at sites of DNA synthesis following strand
  invasion and heteroduplex region at crossover
  sites
• Mismatch repair at heteroduplex

8
Preventing Inappropriate Homologous Recombination

• Potential recombination between repeated
  sequences
• Aborted due to excessive mismatch
• Deletions or gene conversions if allowed to occur

9
Site-specific Recombination
Mobile genetic elements

• moved to nonhomologous sites
• encode enzymes that catalyze mobilization
• recognition of short sequences at ends

10
DNA-Only Transposons

• Transposase recognizes sequences at ends
• Both ends cut and inserted at new site
• Cut-and-paste or replicative pathways

11
Retroviruses

• RNA genome
• Reverse transcription (RNA?DNA)
• Integration of DNA
• Transcription (DNA?RNA)

12
Retroviral-Like Retrotransposons

• Retroviral trans-position mechanism
• Integration of DNA via RNA intermediate

13
Nonretroviral Retrotransposons

• Complex of endonuclease, reverse transcriptase,
  and transposon RNA nicks target DNA
• Free 3-OH as primer for first strand
• Comprise large proportion of human genome