Nucleotide-Excision Repair (NER)

• Damaged bases are removed as oligonucleotides.
• NER is primarily responsible for removal of UV-induced damage and bulky adducts, but also removes ~20% of oxidative damage.
• Deficiencies cause many human disorders.
• Xeroderma Pigmentosum (both classical and variant) and Cockayne's syndrome are caused by defects in NER, resulting in various detrimental effects upon exposure to UV light.

Fig. 29 . a) Nucleotide excision repair; b) base excision repair

DNA Mismatch Repair (MMR)

• Mismatches are removed as long oligonucleotides.
• MMR is primarily responsible for removal of replicative errors.
• Also prevents recombination of non-homologous sequences
• Deficient in many human cancers.
• MMR recognizes base-base mismatch and small insertion/deletion loops.

Fig. 30. DNA mismatch repair

Error prone translation DNAsynthesis

When this pathway is active, DNA repair becomes significantly less accurate and a high mutation rate occurs. It is a part of cellular stress response to extensive DNA damage, also known as SOS response. The cell, at all cases had to survive, so DNA gets repaired, although it contains a lot of errors.

DNA RECOMBINATION

DNA   recombination   involves the exchange of genetic material either between multiple chromosomes or between different regions of the same chromosome. This process is generally mediated by   homology ; that is, homologous   regions of chromosomes   line   up in preparation for exchange, and some degree of sequence identity is required.

• Homologous recombination occurs between two homologous chromosomes.
• Nonhomologous, or illegitimate recombination occurs between two different chromosomes, though the segment at recombination sites may be related.
• Site-specific recombination can result in integration of viral, bacterial, or plasmid DNA into a chromosome at a specific location (such as att).
• Replicative recombination results in sequence transposition, and is mediated by transposase enzymes.

Types of Homologous Recombination

• Reciprocal recombination results from two chromosomes exchanging the same amount of DNA.
• Non-reciprocal recombination results from two chromosomes exchanging different amounts of DNA.
• Intramolecular recombination results from recombination in chromosomal loops.
  • Direct repeats cause plasmid formation from the intervening loop.
  • Inverted repeats cause the intervening loop to change direction.
• Double crossover results in exchanging a short segment of DNA, rather than a large segment of chromosome from the crossover point to the terminus.