3 - Synthesis and Modification of DNA Flashcards
chemical synthesis process
- deprotection of nucleophile (usually hydroxyl)
- base coupling
- capping (optional) - acetylation is done to prevent further chain extension
- oxidation
- cheap process
- synthesized in a 3’ to 5’ direction
biological synthesis process
- DNA is made by DNA polymerase
- synthesized in a 5’ to 3’ direction
- no replication without primer
DNA error checking
- strands dissociate bc they are not complementary
- moves to 3’ to 5’ exonuclease site
primase
synthesized a small piece of RNA
DNA polymerase
replicate DNA
RNA primer
- needed for replication
- destroyed by 5’ to 3’ exonuclease act
ligase
joins the Okazaki fragments by repairing damage from destruction of RNA primer
telomeres
- “buffer zones”
- repeats of TTAGGG sequences
- when telomeres get too short, cell undergoes apoptosis
apoptosis
cell death
DNA methylation
DNA covalently modified with methyl groups
histone modification
- tails that attach to proteins
- alter the activity of DNA
CpG island
region of DNA with many cytosine-P-guanine
epigenetic modification
- information affects gene expression but not encoded within sequence
- example is methylation of CpG (very common)
DNA attack from the inside
- depurination (Gs and As)
- oxidation by ROS
- deamination (amine to carbonyl)
deamination problems
if deamination results in a thymine molecule, there is no way for the cell to know its a mutation
DNA attack from outside
- UV radiation
- alkylating chemicals
aflatoxin B1
- one of the most potent carcinogens
- made by Apergillus fungus which thrives in hot and humid weather
- body will start to oxidize it once it’s identified as a foreign substance
- oxidizes hydrophobic and aromatic molecules to epoxide
calicheamicin
- DNA-targeted toxin
- very reactive
- binds to DNA to form a complex
- releases strain to form an aromatic ring and causes cells to undergo apoptosis
- example is Mylotarg
Mylotarg
- antibody linked to calicheamicin
- in the body, the calicheamicin will be released and it will kill cancer cells
