Biochem - DNA Flashcards
Chromatin
Condensed DNA w/ histones – nucleosome core (histone with DNA wrapped 2x) linked by H1
Histone
H2A x2
H2B x 2
H3 x2
H4 x2
Deamination of cytosine
Uracil
Purines synthesis required substrates
“GAG”
Glycine
Aspartate - N
Glutamine – N
tetrahydroFolate
CO2
“cat PURRR until they GAG and Cough on Fur balls”
Pyrimidine synthesis required substrates
Aspartate
CO2
Glutamine
ATP
Carbamyol phosphate
CPS-2
Carbamoyl phosphate synthase 2
Rate limiting step of pyrimidine synthesis
CPS1 vs CPS2
CPS1:
Urea cycle
In mitochondria
Ammonia source of nitrogen
CPS2:
Pyrimidine synthesis
Found in cytosol
Glutamine source of nitrogen
Draw out prokaryotic DNA replication
Page 516
Exonuclease activity of DNA polymerase
DNA polymerase I and III can add and remove nt from end of DNA strand
DNA polymerase III works 3’-5’
DNA polymerase I:
3’ – 5’ 1 nt at a time
5’ – 3’ 1-10 nt at a time
Eukaryote DNA polymerase alpha
Makes own primer
Replicates 1st 20 nt
Eukaryote DNA polymerase delta
Builds okazaki fragments on lagging strand
Eukaryote DNA polymerase epsilon
Elongates leading strand
Eukaryote DNA poly beta
DNA repair
Eukaryote DNA poly gamma
mt DNA replication
Silent mutation
Genetic code change, same aa
Final polypeptide unchanged
Missense mutation
Change aa sequence
Polypeptide product different structural or functional properities
Nonsense mutation
Base substitution leads to stop codon
Frameshift mutation
Nt added or delated shifting reading frame
Downstream aa sequence completely different
Pyrimidine dimer
2 pyrimidines on same strand of DNA get covalently bonded together
Ts
UV damage
Mismatch repair
Wrong base added
Nick daughter strand up stream
Remove several bases and remake strand and fill in gap created
Nucleotide excision repair
Damaged after creation
Remove entire nt and replace it
Recognizes large bulky areas of damaged DNA
Pyrmidine dimers
Endonucleases remove damaged nt
DNA polymerase fills in gap
DNA ligase joins fragments
Base excision repair
Nonbulky damage just base damaged
Loss of amino group
Oxidized
Methylated
Glycosylase – recognized damaged base – removes damaged base
Lyase – cuts 3’ end of backbone
Endonuclease – cuts 5’ end, removes backbone
Type beta DNA polymerase fills in gaps
Ligase seals it
Double strand repair
Nonhomologous end joining
Clean break in both strands of DNA, gluing back together
Use this if no overlapping segments of DNA
Hereditary nonpolyposis colorectal cancer
Defective mismatch repair
Xeroderma pigmentosum
AR
Defective nucleotide excision repair
Increased risk skin cancer, can’t repair UV damage
Extreme – avoid all sunlight
Bloom syndrome
Mutation in helicase
-DNA replication and repair
hypersensitive to sunlight increased susceptibility to leukemias and lymphomas -immunodeficiency -infertility -facial anomalies
Ataxia-telangectasia
Defective repair of dsDNA breaks
- IgA deficiency
- Ataxia
- poor smooth pursuit of eyes
- high AFP after 8 mo
- sensitive to ionizing radiation
BRCA ½
Defective repair of dsNDA breaks