MBG Part Two: Lecture 13 Flashcards
What does Most DNA Repair Mechanisms require?
Double stranded DNA - as one nucleotide is being repaired, the complementary strand is acting as a template for the repair.
What does DNA repair have built in?
Redundancy: DNA damage can be repaired by more then one mechanism
What Mechanisms can Repair Single Stranded Sequences?
- Mismatch repair
-Direct repair or reversal of DNA damage - Base-Excision Repair
- Nucleotide-Excision Repair
What Mechanisms can Repair Double Stranded Sequences?
- Homology Directed Repair
- Nonhomologous End Joining
What happens during Mismatch Repair
A mismatched nt will occur, a methylation occurs on the old DNA strand (specifically GATC sequence) which allows for the MMR complex to differentiate the old vs new strand.
The MMR brings the GATC sequence an the mismatch close together and nicks the strand at the GATC and Mismatched Base
What does the MMR do?
Degrade the new strand between the nick and the mismatched base
What does exonuclease do?
They remove nucleotides on the new strand between the GATC sequence and the mismatched base
What does DNA ligase and polymeraserase do?
Fill the gaps using the old strand as the template
In Eukaryotes, what does not happen with MMR?
The methylation that occurs on the old DNA strand
What does direct pair fix?
Thymidine Dimers, other specific types of alterations
How can direct repair fix thymidine dimers induced by radiation?
The enzyme photolyase breaks the covalent bonds between dimers when activated by light
How can direct repair, remove a methyl group?
The enymze O6 methyl guanine methyl transferase removes the methyl group from methylguanine , restoring the base back to guanine
What happens in DNA excision repair?
DNA glycosylases can remove the damaged or modified base, removing just the base not the sugar
What does DNA glycosylases leave?
A apurinic or apryimdinic site
What does AP endonuclease do?
Cleaves the phosphodiester bond
What does DNA polymerase do?
Fills in the gaps using the undamaged complementary strand pf DNA as a template
What does DNA ligase do?
Seals the bark (nick) left by DNA polymerase (repair phosphodiester bonds)
What do Nucleotide Excision Repair do?
Remove DNA lesions that distort the double helix
What scans the DNA helix for distortions?
A complex of enzymes
What happens once the distortion has been detected?
Other enzymes separate the DNA and is bound by single stranded binding proteins to keep the DNA apart
What happens to the phosphodiester bond?
It is cleaved
How is the DNA repaired?
Damaged strand is removed by helicase, polymerase fills the gaps, DNA ligase seals the end
What could double stranded breaks in the DNA cause?
Stall replication and could lead to chromosome rearrangements causing deletions, insertions, duplications, and translocations
What are the two pathways to repair doubt stranded breaks?
1.) Homology Directed Repair
2.) Nonhomologous End Joining
What does Homology Dependent Repair do?
Repairs a broken DNA molecule by using the genetic information found in the sister chromatid
- Involves precise insertion
How does Homology Dependent Repair Work?
Enzymes direct strand invasion of unbroken DNA and synthesis occurs; strands are separated re-ligated
What are Non-Homologous End Joining Repair do?
Repairs double stranded breaks independent of a template
When does Non-Homologous Repair Happen?
During the G1 phase when no sister chromatid is present
What are Non-Homologous Repairs more prone to?
Errors such as increased rate of deletion, insertions and translocations
How do proteins fix broken ends?
They recognize the broken ends of DNA and bind them together and can involve polymerases, ligases, nucleases
What rae the proteins that detect the broken DNA?
Ku
A ____ error occurs when a mismatched base has been incorporated into a newly synthesized nucleotide chain. When this DNA is copied, this leads to a _____ error
Incorporation;Replication
The chemical nitrous acid is what type of mutagen?
Deamination Agent
Base Analogs are mutagenic because of which characteristic?
They are similar in structure to the normal base
What type of mutagen is mustard gas?
Alkylating Agent
Depurination can happen spontaneously, which repair mechanism can reverse this?
Base-Excision Repair