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DNA repair mechanisms are grouped into which major categories
Direct repair, excision repair, strand break repair, interstrand crosslink repair, and translesion synthesis
What does direct DNA repair mean
Repair that directly reverses DNA damage without removing nucleotides
What DNA ends are required for DNA ligase to repair a break
A 3’ OH and a 5’ phosphate
What type of damage does photoreactivation repair
UV induced pyrimidine dimers
What enzyme performs photoreactivation in E coli
Photolyase
How does photolyase repair pyrimidine dimers
Uses visible light energy to split the dimer
What lesion is repaired by alkyltransferase
O6 methylguanine
Why is alkyltransferase called a suicide enzyme
It transfers the alkyl group to itself and is not recycled
What is the human equivalent of Ada protein
MGMT
What is excision repair
Removal of damaged DNA followed by resynthesis using the intact strand
What does mismatch repair fix
Replication errors missed by proofreading
Loss of mismatch repair is associated with which disease
Hereditary non polyposis colorectal cancer
What type of DNA damage is repaired by NER
Bulky helix distorting lesions
What are classic examples of NER substrates
Pyrimidine dimers and 6 4 photoproducts
What enzyme complex recognises bulky damage in E coli NER
UvrABC endonuclease
What feature of DNA damage is recognised by NER
Helix distortion not the specific lesion
How many nucleotides are removed in E coli NER
About 12 to 13 nucleotides
What enzyme unwinds DNA during bacterial NER
UvrD helicase
Why is NER energy expensive
It requires ATP for damage recognition unwinding and excision
What human disease results from defective NER
Xeroderma pigmentosum
Why do XP patients have high skin cancer risk
Inability to repair UV induced DNA damage
Which XP proteins act as helicases
XPB and XPD
Which XP proteins make the incisions
XPF ERCC1 makes the 5’ cut and XPG makes the 3’ cut
What is base excision repair used for
Repair of small non bulky base lesions
What enzyme initiates BER
DNA glycosylase
What does a DNA glycosylase remove
The damaged base only
What is an AP site
A sugar phosphate without a base
What enzyme cuts DNA at an AP site
AP endonuclease
Which DNA polymerase fills the gap in human BER
DNA polymerase beta
Why is BER especially important
Many base lesions arise spontaneously
Why excision repair is considered error free
The intact strand is used as a template
Why excision repair cannot fix double strand breaks
No intact complementary strand is available
What are the two main DSB repair pathways
NHEJ and HRR
Which DSB repair pathway is error prone
Non homologous end joining
Which DSB repair pathway is high fidelity
Homologous recombination repair
What is the SOS response
An inducible bacterial DNA damage tolerance response
What triggers the SOS response
Stalled replication forks and single stranded DNA
Which protein senses ssDNA during SOS response
RecA
What happens to LexA during SOS induction
It self cleaves and releases repression
What is the role of LexA
Transcriptional repressor of SOS genes
What is the benefit of the SOS response
Increased survival after DNA damage
What is the cost of the SOS response
Increased mutation rate
What is translesion synthesis
DNA replication across damaged templates
Why is TLS mutagenic
Polymerases insert bases without correct template reading
Does TLS remove the original DNA lesion
No the damage remains
Which polymerase is encoded by dinB
DNA polymerase IV
Why TLS polymerases are tightly regulated
To limit mutagenesis in undamaged cells
Why NER cannot act at replication forks
The DNA is single stranded
What happens if stalled replication is not bypassed
Cell death