Mechanisms Of DNA Repair Flashcards
What are the two general features of DNA repair
- Most repair mechanisms require double stranded DNA: as one nucleotide is being repaired the complimentary strand is acting as a repair template
- DNA repair has built in redundancy
Many types of DNA damage can be repaired by more than one repair system, helps ensure survival
What are the dna repair mechanisms for single stranded sequences
- mismatch repair
- Direct repair or reversal of DNA damage
- Base Excision repair
- Nucleotide-Excision repair
Mechanisms for Repair of double stranded breaks
-Homology directed repair
- Non-homologous end joining
Mismatch Repair (MMR)
A dna repair mechanisms for single stranded sequences
When a mismatched base was added to new strand
The old dna template is methylated
New strand will not
Allows mismatched repair complex (MMR) to differentiate new vs. og strand
It comes in and brings the GATC sequence and mismatch close together
It then nicks the strand at GATC sequence and mismatched bases
MMR degrades new strand btw nick and mismatched based
Polymerase and ligase still the gap using the old strand as a template
Mutations in MMR lead to elevated somatic mutations —> cancer
Direct repair
Restores the original structure of nucleotides:
1. Photoreactivation of UV induced pyrimidine dimers (like 2 Ts on same strand stuck together)
Photolyase breaks the covalent bonds between dimers when activated by the absorption of blue light
- The enzyme O6-methylguanine-DNA methyltransferase removes the methyl group from O6methylguanine, restoring the base to guanine
Base excision repair
A dna repair mechanisms for single stranded sequences
Removal and replacement of modified bases:
- dna glycosylases recognizes and excises/removes the damaged base or bases. Just the base is removed, not the deixiribose sugar
- these enzymes are specific for each modified base (delaminated based, hypoxanthine, etc.)
- produces an apurinic or apyrimidic site (AP site)
- AP endonuclease cleaves the phosphodiester bond in the 5’side of the AP site
- Other enzymes remove the deoxiribose sugar
- A dna polymerase fills in the gap, using the undamaged complementary strand of DNA as a template
- Dna ligase seals the nick left by dna polymerase
Nucleotide excision repair (NER)
dna repair mechanisms for single stranded sequences
Removes dna lesions that distort the double helix
There is a complex of enzymes that scans dna helix for distortions in 3-D configuration
Once detected, other enzymes separate the dna and single stranded binding proteins stabilize the strands and keep them apart
An enzyme cleaves Phosphodiester bonds on either side of the mutation
Damaged strand is removed by dna helicase
Gap is filled in with dna polymerase
Ends are sealed by dna ligase
Helicase role in NER
In nucleotide excision repair, Damaged strand is removed by dna helicase
What is Xeroderma pigmentosum an example of
Mutation of human NER genes
Do double stranded breaks cause mutations?
By themselves, no
But they stall dna replication and can lead to chromosomal rearrangements, which in turn can cause deletions, duplications, inversions and translocations
Homology dependent repair
Method of double stranded dna break repair
Aka homologous recombination
Repairs a broken dna molecule by using the genetic information contained in the sister chromatid
Employs the same system as in homologous recombination that occurs during crossing over during meiosis
How does homology dependent repair work?
Removal of nucleotides at broken end
Enzymes (ex. BRCA1, 2) direct strand invasion of unbroken DNA (of sister chromatid) and synthesis occurs
Strands are separated and religated
The 3’ end elongates further displacing the original strand
The displaced strand forms a loop that’s base pairs with the broken dna mlc
Dna synthesis is initiated at the 3’ end of the bottom strand and the displaced loop is being used as a template
Strand attatchment produced two Holliday junctions, each can be separated by cleavage and reunion
Nonhomologous end joining (NHEJ)
Repairs double stranded breaks
Doesn’t use homologous template
Happens during G1 phase of the cell cycle, when no sister chromatid is present
Proteins that recognize broken ends of DNA just bind them together
More error prone, so have increased rate of deletions, insertions and translocations
Also involves dna polymerase, nucleuses and ligases
What are Ku
The proteins that detect the promenade dna in nonhomologous end joining repair of double stranded breaks
Nonhomologous end joining (NHEJ)
Repairs double stranded breaks
