chapter 5.3 Flashcards
colon cancer
mismatch repair
skin cancer
nucleotide excision repair
what are two most frequent spontaneous chemical reactions that cause serious DNA damage in cells
depurination and deamination
deamination of adenine
hypoxathine
deamination of guanine
xanthine
deamination of cytosine
uracil
deamination of thymine
NONE
what is deamination (for dummies)
the removal of an amine group from a base
note: if the normal C is paired with a G and is then deaminated, it will become a U. then, this U will be replicated and paired with an A and then this sequence is mutated
is deamination spontaneous
yes!
note: it is estimated to occur 100 times per day in every human cell
deamination can lead to……
point mutations if not corrected
how is deamination fixed
base-excision repair
what is depurination (for dummies)
the loss of a purine base (A or G)
the A or G is cleaved out at AP (apurinic) sites
what usually happens as a result of depurination
transversions! the missing base is normally replaced with a T
is depurination spontaneous
yes!
when does base excision repair occur
prior to DNA replication
when does mismatch excision repair occur
mainly post DNA replication
when does nucleotide excision repair occur
prior to DNA replication
when does proofreading by DNA polymerase occur
during DNA replication
what does non-homologous end joining and homologous recombination fix
double stranded DNA breaks
what are the main enzymes in base excision repair
DNA glycosylase - cut out wrong base (chop it out)
APEI endonuclease + AP lyase- cut out backbone
DNA Pol Beta + DNA ligase - add the correct base back in and repair the backbone (sew everything back up together and make it look cute again)
what enzyme recognizes the unusual nucleotides and how does it do this
DNA glycosylases and base flipping
what is base flipping (for dummies)
DNA glycosylase flips a base completely out of the double helix to check it out when it thinks it’s the wrong base paired into the helix
what does mismatch excision repair fix
errors that remain in DNA after proofreading by DNA polymerase
what are the steps of mismatch excision repair
- removal of the mutation by a nuclease
- gap filling by DNA polymerase
- sealing of the nick by DNA ligase
what kind of damage does UV radiation cause
pyrimidine dimers
what are thymine dimers + how do they happen (for dummies)
UV radiation gets thymine overly excited and makes it want to bond with its friends so it creates a C-C bond between itself and an adjacent thymine (its friend)
what do T-T dimers interfere with
replication and transcription
what mechanism fixes T-T dimers
excision repair
what does nucleotide excision repair fix
DNA regions containing chemically modified bases that distort the normal shape of DNA
how does DNA synthesis get around DNA lesions
DNA lesions cause DNA replication to stall so DNA polymerase delta or epsilon are momentarily switched out for an error-prone DNA polymerase that simply overlooks the bump in the DNA and moves right along and the lesion is bypassed!
after, the polymerases switch back
this is called translesion synthesis
what is the difference between base excision repair and nucleotide excision repair
BER - one single base
NER - often chunks of the backbone to fix pyrimidine dimers
nonhomologous end joining
- synapse forms at the broken ends of the double-stranded break by DNAPK
- nucleases remove bases from the DNA ends
- the two molecules are ligated together with several base pairs missing
note: error prone because base loss causes genetic mutation and incorrect rejoining can cause chromosomal rearrangment
nonhomologous end joining (for dummies)
at the double stranded break, DNAPK (“dna pick”) comes and PICKS the two molecules up, cuts the torn ends so they line up, and sews them together without caring what is cut off (error prone)
homologous recombination
genetic exchange at equivalent positions along two chromosomes with substantial DNA sequence homology
how does homologous recombination fix DNA damage
causing the exchange of large regions of chromosomes between the maternal and paternal pair of homologous chromosomes
