Lecture 23 Flashcards
DNA Damage and Repair
mutations
a change in the DNA structure that can change the genetic code and cause damage
examples of environmental factors that cause mutations
- UV
- radiation
- chemical agents
what are the 3 types of point mutations?
All substitution mutations
- silent - same protein is made
- nonsense - no protein is made
- misuse - the wrong protein is made
What do point mutations cause?
base substitutions
What are the 2 types of substitutions caused by point mutations
- translation
- tranversion
what are the two types of mutations?
- point mutations (one base switch)
- insertions/ deletions (one or more bases)
How does base mismatch occur?
when the template strand has been damaged
transition
when a purine is replaced with the other purine, causing to pair with the wrong type of pyrimidine or vice versa.
The most common substitution
transversion
least common substitution, a purine is replaced with a pyrimidine or vice versa
chemical mutagens that cause point mutations
- deaminating agents
- alkylating agents
deamination
chemical agent, like nitrous acid, removes the NH2 and now its an O
eg. A->A* so now A-C instead of A-T (A* is basically a G)
A* is now called hypoxanthine
what type of repair fixes deamination?
base pair excision
alkylation
chemical agent adds a methyl/ethyl group to a purine.
eg. G->G* so now G-T instead of G-C. (G is basically a A)
G* is now called O6-alkylguanine
what causes deamination and alkylation
usually chemicals in high processed food. for alkyltaion, a metabolic error can produce reactive O2
chemical mutagens that cause insertion/deletions
intercalation agents - goes in between base pairs may cause another to be deleted or inserted
what does UV damage do and what is the issue?
it causes adjacent Thymine pairs to bond together instead of the double bonds. called cyclobutane ring.
it is an issue because it makes it harder to separate the base pairs in order for replication
how does UV damage get repaired
in plants, an enzyme called photolyase does a direct repair to fix it. Humans do not have that so instead a nucleotide excision occurs
xeroderma pigmentosum
disorder when people do not have proper nucleotide excision genes. they can not go into the sun
oxidative damage
metabolic error causes reactive oxygen species. Hydroxyl radicals is the worse. it is repaired by DNA glycosylases with is a base excision repair
Direct Repair and example
damaged bases are repaired on site
eg. photolyase for thymine dimers or O6-alkylguanine alkyltransferase for added methyl groups.
Base excision repair and example
offending base is removed and replaced
eg. glycosylase and DNA pol 1 for deamination
Nucleotide excision repair and example
a whole row of nucleotides are damaged so removed and replaced
eg UV damage is removed by exinuclese and replaced by DNA pol 1
Mismatch Repair
the wrong nucleotide is added during replication so the daughter strand must be identified and distinguished from the template strand and replaced.
- Enzymes MutL & MutS fid the error and identify the template strand with the methyl group on it.
- MutH cuts daughter strand from template methyl group
- portion is removed by exonuclease
- replaced by DNA pol 3
Homologous recombination
repairing a break in double strand
which is the only repair that uses DNA pol 3
Mismatch Repair
