DNA DAMAGE
spontaneous dna damage
-Sites that are known to be modified by spontaneous oxidative damage, hydrolytic attack, and uncontrolled methylation are shown, with the width of each arrow indicating the relative frequency of each event
depurination and deamination
-these two runs are the most frequent spontaneous runs known to create serious DNA damage in cells. -Depurination affects both purines and deamination an occur on other nucleotides as well as cytosine
Nucleotide excision repair
A large multi enzyme complex scans the DNA for distortions in the felix (rather than fora single base pair) - A cut is made on either side of the distortion by an enonuclease and an associated DNA helicase then removes the entire portion of the damaged strand - the large gap (15-27 nucleotides in eukaryotes) is repaired by DNA polymerase and DNA ligase bigger
Chemical Damage to DNA
DNA adducts are chem groups that are added onto the DNA as a consequence of high exposure to a mutagenic chem. example: benzo alpha pyrene cigs not carcinogenic until its oxidized within cells then it can covalently bind to guanine residues in dna, interrupting hydrogen bonding in g-c pairs
base excision repair
a family of endonucleases known as the DNA glycolyases recognizes altered bases and remove them.. an ap endunuclease recognizes that the deoxyribose lacks the base and removes sugar in conduction with phosphodiesterase. DNA polymerase and DNA ligase fill in the missing base using the opposite strand as the template little stuff
Thymine dimer
covalent bonds between adjacent pyrimidines, particularly thymines, as a result of ultraviolet light such as sunlight. this causes problems for DNA replication as the dimers can not be recognized by DNA polymerase
base excision repair pathways
daminated c in dna hydrogen bonded base pairs uracil dna glycolyase DNA helix with missing base AP ENDONUCLEASE and remove sugar phhosphate DNA helix with single nucleotide gap DNA polymerase adds new nucleotides, DNA ligase seals nick
Mutations
distort the double helix because newly mutated base does not base pair with its partner correctly
how does smoking cause cancer
nicotine
addiction
addictive bc over stimulation of the receptor causes the receptor to be desensitized over production of dopamine cases a decrease in the dopamine production. in response,brain cells produce more copies of the receptor protein. larger ants of nicotine are needed to get the same effect
Uncorrected depurination
can lead to either the substitution or the loss of a nucleotide pair when the replication machinery encounters a missing purine on the next template strand, it may skip to the next complete nucleotide, producing a deletion missing a base pair going through replication it'll leave it blank causing 1 base deletion problem
DNA repair pathways
each cell contains multi DNA repair systems, each with its own enzymes and preferences for the type of damage recognized. most of these use the undamaged strand of the double helix as a template repair the damaged strand.. the two major repair pathways are base excision repair and nucleotide excision repair
nicotine
not carcinogen cell attempts to detoxify the compounds using a set of enzymes called cytochrome p450s -as these enzymes are metabolized when you detoxify turn into carcinogens
deamination
occurs on all bases except thymine (thymine doesn't have extra cyclic group) deamination of cytosine to uracil is the most coming w a rate of about 100 bases per cell per day make cytosine into uracil because amino group replaced with ketone its h group acceptor changed H bond identity - the amino group is replaced with a ketone thus deaminated cytosine becomes a uracil glutamate to alpha ketogluterate vis glutamate dehydrogenase
uncorrected deamination
of cytosine results in a substitution mutation when the dna is replicated an adenine will be inserted instead of a guanine
DNa repair pathways
other repairs ystems repair double stranded breaks in the DNA helix double stranded breaks would be disastrous because they would quickly lead to the breakdown of chromosomes -thus they are repaired at any price, sen the loss genetic info
Depurination
process whereby purine bases (ag) are lost bc their n-glycosyl linkages to deoxyribose are spontaneously hydrolyzed -about 5000 purine bases per cell per day are lost this way
Non-homologous end joining
the break is repaired by DNA ligation but some nucleotides are lost at the break site. this is better than letting the chromosome break ,especially as so little of human DNA encodes protein region with altered segment due to missing nucleotides
Homologous end joining
the break is repaired with fewer problems bc the gap is filled in by copying from the second chromosome this run involves special recombination proteins that recognize areas of matching DNa sequence between 2 chromosomes complete sequence restored by copying from second chromosome
Radiation Damage to DNA
ulta violet light can cause covalent linkages between adjacent pyrimidines, known as pyrimidine dimers or aka thymine dimers ionizing radiation, x ray gamma rays causes double stranded breaks in dna
