Lecture 4 - DNA repair Flashcards
Types of DNA damage
3 classes: single-base changes, structural distortions / bulky lesions and strand breaks
Single-base changes
Affect the sequence but do not grossly distort the overall structure -> do not affect transcription or replication.
Repair mediated by replication-linked mismatch repair system.
Structural distortions / bulky lesions
Introduction of covalent links between bases on one strand -> inhibit replication and transcription.
Repaired by photoreactivation.
Photoreactivation
Reversing inappropriate covalent bonds to undo damage of structural distortions.
Abasic site
Base is missing, but backbone intact
Nick
Phosphodiester backbone is broken on one strand - base intact
Base-excision repair
Directly removes the damaged base and replaces it - backbone intact.
Mismatch repair
Detects mismatch – the methylated strand is recognised as the “right one” and thus used as template – the other nucleotide is removed (whole nucleotide).
Nucleotide-excision repair
A sequence containing the damaged base is excised (whole nucleotides) and a new strand of DNA is synthesised for replacement.
Homologous recombination repair vs Non-homologous end-joining
Recombination repair:
Needs a template - homologous strand
Avoids mistakes - ensures that no genetic information is lost.
Slow, high use of ressources. If NHEJ does not get to repair the error, it is nice to have recombination repair.
NHEJ: risk of combining the ends wrongly. Always used when no homologous chromosome is not available.
Quick - DSB only exists shortly. Few proteins involved.
DNA DSB repair
Homologous recombination repair and Non-homologous end-joining
Holliday junction
An intermediate in homologous recombination in which the two duplexes of DNA are connected by the genetic material between two of the four strands - one from each duplex.