Lecture 11 Flashcards
Point mutations is a – level base substitution
DNA
replace DNA base with the same chemical property
purine–> purine
transitions
replace DNA base from different chemical
property
purine –> pyrimidine
transversions
one or more DNA nucleotides are added
base insertions
one or more DNA nucleotides are deleted
base deletions
Base substitutions in coding regions is – level
amino acid
change mRNA nucleotide but same aa
silent mutation
change mRNA nucleotide change aa
missense mutation
change mRNA nucleotide –> stop codon
nonsense mutation
altered aa is in the same aa group
conservative missense mutation
altered aa is in a different aa group
non-conservative missense mutation
DNA damage is unavoidable and arise by – of chemical bonds in DNA
spontaneous cleavage
DNA damage can occur via – chemicals in the environment
genotoxic
DNA damage can occur via certain by-products of normal –
cellular metabolism
DNA damage can occur via environmental agents such as – and -
UV light and ionizing radiation
DNA damage can occur via – induced by DNA pol during replication
copying errors
inside the cell is - environment
reducing
deamination of a cytosine base, converts it into a
uracil
deamination of a common modified base 5-methyl cytosine, converts it to a –
thymine
depurination can release – and – from a DNA strand
guanine and adenine
depurination can a – mutation
deletion
common type of damage caused by UV light
thymine dimers
thymine dimers interfere with – and –
DNA replication and RNA transcription
cells use – to fix DNA regions containing chemically modified bases that distort the normal shape of DNA locally
nucleotide excision repair
determine potential mutagens
Ames test
base analog of thymine that can bind with guanine
5-bromouracil (enol tautomer)
intercalating agents that can cause mutations include
proflavin, ehtidium, and acridine orange
first line of defense in preventing mutations is
DNA polymerase
proofreading depend on the – of some DNA pol
3’–> 5’ exonuclease activity
when an incorrect base is incorporated during DNA synthesis, the 3’ end is transferred to the – where the incorrect misfired base is removed
exonuclease site
– methylates A residues of 5’GATC3’ sequence
E. coil dam methylase
methylation marks the – therefore the mismatch repair system can distinguish the newly synthesized strands
template strands
– enables replication to proceed across DNA damage
translesion DNA synthesis
in photoreactivation, – breaks thymine dimers
DNA photolyase
methyl group removal by – is an example of direct reversal of DNA damage
methlytransferase
besides DNA pol, cells have other repair systems called – for preventing mutations due to copying errors and exposure to mutagens
DNA excision-repair systems
many cancers arise from a loss of one of –
DNA repair systems
base excision repair removes damaged bases by a specific
glycosylase
Because a G-T mismatch is almost always caused by a chemical conversion (deamination) – the repair system “knows” to remove the – and replace it with –
5-methyl C –> T
remove T and replace with C
– is recognized by a DNA glycosylase and flips out the thymine base out of the helix cuts it away from the sugar-phosphate backbone
G-T mismatch
– an endonuclease specific for the 5’ end of the baseless site cuts the DNA backbone
APEI
another endonuclease called – which is associated with DNA pol beta removes the deoxyribose phosphate
AP lyase
– fill the gaps which are sealed by DNA in base excision repair systems
DNA pol beta
in nucleotide excision repair, a complex of – and – proteins slide along the surface of a double stranded DNA molecule looking for any distortions of the double helix.
XP-C and 23B
complex of XP-C and 23B recruits then recruits the general transcription factor –, whose helicase subunits partially unwind the double helix.
TFIIH
After TFIIH is recruited, – then bind to the complex and further unwind and stabilize the helix until a bubble of ~25 bases is formed.
XP-G and RPA proteins
After a bubble is formed, –(now acting as an endonuclease) and –, a second nuclease, cut the damaged strand on each side of the lesion.
XP-G and XP-F
during nucleotide excision repair, the DNA fragment with damaged bases is released and –
degraded to mononucleotides
Lastly, the gap is filled by –, and the remaining nick is sealed by DNA ligase during nucleotide excision repair
DNA polymeraseδ/ε
error – homologous recombination
free
error – DNA end joining
prone
error- free homologous recombination: double strand DNA break forms in the –
chromatids
error-free homologous recombination: double strand break activates – which leads to the activation of a set of exonucleases that remove nucleotides at the break creating single-stranded 3’ ends
ATM kinase
error-free homologous recombination: in a BRCA1 and BRCA2 dependent process, – polymerizes on single-stranded DNA with free 3’ ends to form a nucleoprotein filament
RAD51
error-free homologous recombination: – conducts a homology search on the duplex DNA sequence in the sitter chromatid
RAD51 nucleoprotein filament
after finding a homology, the RAD51 nucleoprotein filament invades the duplex to form a – in which the single-stranded 3’ end is base-paired to the complementary strand on the homologous DNA strand.
joint molecule
error-free homologous recombination: DNA pol elongates the 3’ end of the – (using the complementary sequences on the sister chromatid as a template)
damaged DNA
error-free homologous recombination: When sufficiently long, this repaired 3’ end of the damaged DNA – with the single-stranded end of the other damaged strand.
pairs
error-free homologous recombination: Any remaining gaps are filled in by DNA polymerase and DNA ligase, regenerating a – double helix in which an entire segment has been regenerated.
wild-type
The predominant mechanism of double-strand break repair in multicellular organisms.
error-prone repair by enjoining
error-prone repair by enjoining: nvolves rejoining the – of two DNA molecules.
nonhomologous ends
error-prone repair by enjoining: Even if joined DNA fragments come from the same chromosome, the repair process results in loss of several base pairs at –(mutations).
the joining point
error-prone repair by enjoining: -Sometimes broken ends from different chromosomes are accidentally joined together, leading to – of pieces of DNA from one chromosome to another.
translocation
