Lecture 9 - DNA damage and repair Flashcards
name the 5 sources of DNA damage
normal metabolism (free radicals)
UV light
ionising radiation
DNA synthesis
environmental mutagens
when UV light damages DNA what happens to pyrimidine dimers?
they fuse, strands break, produces pyrimidine photoproducts (6-4)
name 3 sources/types of ionising radiation that cause DNA damage
solar
cosmic
terrestrial radionuclides (C14, H3)
which molecule, when unrepaired, mispairs with A and causes G-T transversion mutations in the generation of oxidative damage?
8-oxodG
8-oxodG has which 2 groups coming off the 2 main rings (hexagon and pentagon)? which ring does each group come off?
double bond O coming off pentagon
NH2 coming off hexagon (as well as a double bond O)
what is a major source of radon giving off natural exposure?
uranium in granite
name 5 sources of environmental mutagens
food, water, air borne, smoking, industrial
what are 2 examples of environmental mutagens causing DNA damage in food?
acrylamide, aflatoxin
what are 2 examples of environmental mutagens causing DNA damage in the air?
car exhaust fumes, polycyclic aromatic hydrocarbons
what is an example of environmental mutagen causing DNA damage in water?
heavy metals
name 4 foods aflatoxin, an environmental mutagen causing DNA damage, is found in
dried fruits, corn, peanuts, grain
true or false, aflatoxin is highly mutagenic, carcinogenic and hepatotoxic?
true - can cause liver cancer
acrylamide in food comes from what?
high temp cooking - from asparagine
name the 5 DNA repair mechanisms
direct reversal, NER, BER, mismatch repair, DSB repair
which DNA repair mechanism, when it involves photolyase, is not found in humans?
direct reversal
in direct reversal DNA repair the methylation of adenine and cytosine is done by what? the methylation of guanine is done by what?
A/C - ABH2/ABH3
G - MGMT
In direct reversal of DNA damage, what is specifically repaired? which functional group is transferred to it?
06methylguanine
methyl group
direct reversal of DNA damage is used when damage sources are which 3 things?
exogenous alkylating agents, normal metabolites and therapeutic exposure (chemo)
which method of DNA damage repair is the primary mechanism for repair of UV induced or chemical induced damage?
nucleotide excision repair
how many bases does NER remove?
24-29
what are the 2 types of NER?
global genome and txn coupled
which progeria syndrome is a result of transcription coupled NER repair failure?
cockayne syndrome
which mechanism of DNA repair is the main mechanism for repair of oxidative damage, deamination, depyrimidation?
base excision repair
in base excision repair there are two types what are they? how many bases do they repair each
short patch (1bp) and long patch (2-12bp)
in base excision repair damage recognition is done by which DNA enzyme?
DNA glycosylase
which DNA glycosylase recognises damage for 8-oxodG in base excision repair?
hOGG1
which DNA repair mechanism is the primary mechanism for recognition of DNA
mismatches and chemically induced damage arising during DNA replication?
mismatch repair
mutations in which DNA repair pathway are associated with
familial colon cancer? what are the mutations?
mismatch repair, MLH1 and MSH2
name the 2 types of DSB DNA repair?
NHEJ and homologous recombination
NHEJ and homologous recombination repair double strand breaks that arise during which 3 things?
replication, from chemical damage and ionising radiation
what are the 4 alternatives to DNA repair mechanisms?
activation of signalling systems, cell cycle arrest, apoptosis and senescence
