Dna Repair And Recombination Flashcards
What is mismatch repair?
Responsible for repairing errors introduced during DNA replication. This error correction refines replication fidelity by an additional 10^2 or 10^3. Mechanism The newly generated strand lacks methylation marks present in the template strand, allowing determination of the correct sequence (mediated by the Mut proteins). DNA is also methylated in humans, but the mechanism of recognition of the template strand is still unknown -An endonuclease nicks the strand followed by exonuclease degradation -DNA Pol III and DNA ligase fill in the lost
DNA Hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch syndrome can be caused by mutations in mismatch 24 repair predominantly. About 5% of colon cancer is caused by HNPCC
How many human nucleotides are damaged per day per human cell?
It is estimated that 10,000 to 1,000,000 nucleotides are damaged per human cell per day by spontaneous chemical processes such as depurination, demethylation, or deamination; by reaction with chemical mutagens in the environment; and by exposure to ultraviolet or ionizing radiation.
What is nucleotide-excision repait?
Responsible for repairing DNA lesions that produce large distortions in the DNA double helix, such as pyrimidine (usually thymine) dimers caused by UV radiation
Mechanism:
Excinuclease – a nuclease capable of making two specific endonucleolytic cleavages, compare to the one made by standard endonucleases. This enzyme recognizes the damage and nicks the strand on either side of the damage
DNA polymerase I and DNA ligase fill in the lost DNA
Xeroderma Pigmentosum is caused by mutation of proteins involved in nucleotide-excision repair –unable to repair dna damaged by UV light
–dna contains cytosine, not uracil bc spontaneous deamination.
What is Base-excision repair?
Responsible for repairing abnormal bases that can
occur due to spontaneous deamination of cytosines to
uracils, deamination of adenine to hypoxanthine and
other base damaging reactions
Mechanism:
- A uracil glycosylase recognizes and removes the
uracil base, leaving an apyrimidinic (AP) site in
the DNA strand
- An AP endonuclease nicks the backbone of the
damaged strand at the missing base
- Deoxyribose phosphate lyase removes the base
free phosphate residue
- Additional nuclease action removes a few more
bases and the gap is filled in by DNA polymerase I
- DNA ligase seals the nick in the repaired stran
What is Direct repair?
Class of repair where enzymes are dedicated to repairs of specific types of damage
Responsible for repairing pyrimidine dimers in bacteria in a process known as photoreactivation
Mechanism varies depending upon enzyme but involves just the specific enzyme
-Direct repair of O6–methylguanine is carried out by O6–methylguanine DNA methyltransferase
What are double stranded break repair mechanisms?
Double stranded breaks are caused by high-energy radiation or oxidative free radicals
Nonhomologous end-joining is the more error prone of the mechanisms because it is associated with deletion of DNA
-Defects are associated with cancer predisposition and immunodeficiency syndromes
Homologous recombination repair uses the enzymes involved in homologous recombination in meiosis
–CRSIPR technique
What is Recombination?
Recombination refers to the rearrangement or exchange of genetic information between two DNA molecules or between two different parts of the same DNA molecules
What is legitimate DNA recombination?
Legitimate DNA recombination – the recombination event occurs at aligned points on the genetic map, so that no information is lost. This occurs in regions of high homology
-Formation of a Holliday junction occurs
Example: “Crossing over” between pairedhomologous chromosomes during meiosis
What is Illegitimate DNA recombination and examples?
Illegitimate DNA recombination – recombination occurs between DNA segments not aligned on the genetic map
Examples:
- “Unequal crossing over” of chromosomes
- Integration of viruses into host DNA
- Rearrangement of Immunoglobulin genes during differentiation in precursor cells and B lymphocytes
- The movement of transposons or “mobile genetic elements” from one site to another
