dna repair part 2

• photoreactivation

  repairs pyrimidine dimer in bacteria,

  DNA photolyase captures energy from light and use it to break the ring formed between the dimers to restore two thymine residues

  methylguanine can be demethylated and reversed to restore a guanine. the methyl group is transferred to a cysteine in the enzyme
• base excision repair

  DNA glycosylase recognize a oxoG:A mismatch and replaces the non-damaged A for C. the unnatural/damaged base is cleaved out by specific glycosylase. the strand is the synthesized by DNA pol I and DNA ligase
• nucleotide excision repair steps:

  recognition: UvrA

  excision: UvrC and UvrD (and help form UvrB-induced bubble)

  ligation: DNA ligase
• base excision repair steps:

  recognition: DNA glycosylase

  DNA synthesis: DNA pol I

  ligation: DNA ligase
• mismatch repair system steps:

  recognition: MutS and MutH determines the strand

  excision: MutH (activated by MutL) and exonuclease

  DNA synthesis: DNA pol III

  ligation: DNA ligase
• DSB repair: mammalian pathway for NHEJ

  recognition: heterodimer Ku70+Ku80 binds to broken ends and recruits protein kinase DNA-PKcs

  excision: DNA-PKcs forms a complex with Artemis which has both exonuclease and endonuclease activity activated by phosphorylation

  DNA synthesis: no synthesis, the complex makes the ends processed and ready for ligation

  ligation: ligase IV performs ligation in a complex with XRCC4 and Cernunnos-XLF
• DSB repair: homologous recombination

  Recombination repairs DNA breaks by retrieving sequence information from undamaged DNA, in the sister chromosome or from the other replicated strand
• DSB repair: non-homologous end joining

  When there is not a sister chromosome or replicated strand to retrieve info from. NHEJ protects, processes and join ends together. Sequences across the break is lost. NHEJ may thus be mutagenic.
• what is translesion DNA synthesis

  one mechanisme for when DNA repair is not possible and a fail-safe system is triggered allowing the replication machinery to bypass the lesion and thus tolerate the damage. the damage remains (possibly repaired later) but replication is saved
• translesion synthesis control in mammals (models):

  pol-switching model: Once ubiquitinylated, the sliding clamp recruits a translesion DNA pol.

  gap-filling model: The DNA pol skips over the lesion, continuing synthesis downstream. A translesion DNA pol. comes in later and repair the gap.