DNA repair and recombination
May 11, 2015
DNA repair and recombination
Spontaneous Alterations of nucleotides
Red: oxidative damage; blue: hydrolytic attack; green: uncontrolled methylation
Depurination and deamination
Spontaneous Damage to DNA
Spontaneous Damage to DNA
Examples of DNA Damage Induced by Radiation and Chemicals
Examples of DNA Damage Induced by Radiation and Chemicals
Examples of DNA Damage Induced by Radiation and Chemicals
Mutation Generation passed on to daughter DNAs
Mutation Generation passed on to daughter DNAs
Direct Repair of Thymine Dimers
Repair of O6-Methylguanine
Repair of O6-Methylguanine
Base-Excision Repair
Base-Excision Repair
Nucleotide-Excision Repair of Thymine Dimers
Nucleotide-Excision Repair of Thymine Dimers
Mismatch Repair in E. coli
Eukaryotic DNA PolymerasesEnzyme Location Function
• Pol α (alpha) Nucleus DNA replication– includes RNA primase activity, starts DNA strand
• Pol δ (gamma) Nucleus DNA replication– replaces Pol α to extend DNA strand, proofreads
• Pol ε (epsilon) Nucleus DNA replication– similar to Pol δ, shown to be required by yeast mutants
• Pol β (beta) Nucleus DNA repair• Pol ζ (zeta) Nucleus DNA repair• Pol γ (gamma) Mitochondria DNA replication
General Recombination
• Two homologous DNA molecules cross over
• The site of exchange can occur anywhere
• A strand of one DNA molecule has become base-paired to a strand of the second DNA to create heteroduplex joint
• No nucleotide sequences are altered
Recombination at the Molecular Level
• Breakage and joining also directed by enzymes.
• Homologous recombination occurs during synapsis in meiosis I, general recombination in bacteria, and viral genetic exchange.
• Molecular mechanism proposed by Holliday and Whitehouse (1964).
• Depends on complementary base pairing.
RecA protein-mediated DNA synapsisRec A has multiple DNA binding sites, hence can hold a single strand and a double helix together
Rec A is also a DNA-dependent ATPase
Salmonella typhimurium can change protein in flagella (flagellin)Phase variation
Replicative transposition – the element moves a copy of itself to a new site via a DNA intermediate
Conservative transposition – the element itself moves from the donor site into the target site
Retrotransposition – the element makes na RNA copy of itself which is reversed transcribed into a DNA which is then inserted
When IS elements get it together:composite transposons
�������������� �����������������������������
������������