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91 Cards in this Set

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What are the charges of DNA and histones?
DNA is negative
Histones are positive
What is a nucleasome?
2 loops of DNA around a histone octamer
What is unique about H1?
only histone not part of nucleosome
links nucleosome beads in a string
What is heterochoromatin?
HeteroChromatin = Highly Condensed
What are the methylated nucleotides (2)?
cytosine, adenine
What is the function of methylation in DNA replication?
distinguishes template (methylated) strand from new strand
What is the purpose of hypermethylation?
inactivates DNA from transcription
What is accomplished with histone acetylation?
Acetylation --> Active DNA

relaxes coiling for transcription
purines
# of rings?
adenine, guanine

PUR As Gold

2 rings
pyrimidines
# of rings?
CUT the PY

cytosine, uracil, thymine

1 ring
which nucleotide bond is stronger?
G-C bond is stronger than A-T

3 H-bonds vs. 2 H-bonds
What are the components of a nucleoside?
base + ribose
What are the components of a nucleotide?
base + ribose + phosphate

3'-5' phosphodiester bond
What are key features of purine synthesis?
start w/ sugar + phosphate (PRPP)

add base
What are key features of pyrimidine synthesis?
temporary base: orotic acid

add sugar + phosphate (PRPP)

modify base
pryimidine production requirement (1)
aspartate
purine production or reuse requirements (4)
aspartate
glycine
glutamine
THF
What is done by ribonucleotide reductase?
converts ribonucleotides --> deoxyribonucleotides

(UDP to dUDP)
Which pathways have carbamoyl phosphate? (2)
1. de novo pyrimidine synthesis

2. urea cycle
What occurs with ornitine transcarbamoylase deficiency?
OTC is in urea cycle

deficiency --> accumulated carbamoyl phosphate converted to orotic acid in pyrimidine synthesis pathway
How does hydroxyurea work?
antineoplastic drug

inhibits ribonucleotide reductase
What is the function and mechanism of 6-mercaptopurine?
immunosupressive drug

blocks de novo purine synthesis
What are the function and mechanism of 5-fluorouracil?
antineoplastic

inhibits thymidylate synthase (decreases dTMP)
What does thymidylate synthase do?
converts dUMP to dTMP in pyrimidine synthesis
What is the function and mechanism of methotrexate?
antineoplastic drug

inhibits dihydrofolate reductase (lowers dTMP)
What does dihydrofolate reductase do?
converts DHF to THF for use in conversion of dUMP to dTMP
What is the function and mechanism of trimethoprim?
antibiotic drug

inhibits bacterial dihydrofolate reductase (lowers dTMP)
What is orotic aciduria?
inability to convert orotic acid to UMP

autosomal recessive
What are the causes of orotic aciduria? (2 possible enzyme defects)
orotic acid phosphoribosyltransferase

orotidine 5'-phosphate decarboxylase
What are the features of orotic aciduria?
orotic acid in urine
megaloblastic anemia (unresponsive to B12 or folic acid)
failure to thrive
What is the treatment for orotic aciduria?
oral uridine
What are features of ornitine transcarbamylase (OTC) deficiency?
increased orotic acid AND hyperammonemia
What occurs in adenosine deaminase deficiency?
--> SCID

excess ATP and dATP imbalances nucleotide pool --> inhibition of ribonucleotide reductase

low lymphocyte count
What does adenosine deaminase do?
in purine salvage pathway

converts adenosine to inosine
What causes Lesch-Nyhan syndrome?
absense of HGPRT in purine salvage pathway

X-linked recessive

excess uric acid and de novo purine synthesis
What are the features of Lesch-Nyhan syndrome?
retardation
self-mutilation
agression
hyperuricemia
gout
choreoathetosis
What is choreoathetosis?
involuntary movements with chorea (migrating contractions) and athetosis (twisting and writhing)
What are the 2 non-redundant codons?
AUG: methionine (START)

UGG: tryptophan
What organisms can have genetic code that is NOT commaless/nonoverlapping?
some viruses
What are the origin points for eukaryotic DNA replication?
consensus sequences
What do single-stranded binding proteins do?
prevent strands from reannealing during replication
What do DNA topoisomerases do?
create nicks in DNA helix to relieve torsion/supercoils during replication
What is DNA gyrase?
prokaryotic topoisomerase II
What is the function and mechanism of fluoroquinolones?
antibiotics
inhibit DNA gyrase
What is the function of primase?
makes RNA primer for DNA polymerase III to initiate replication on the lagging strand
What does DNA pol III do?
prokaryotic

elongates leading and lagging strands (latter up to RNA primer)
Which DNA pol has 3'-->5' exonuclease activity for proofreading?
DNA pol III
What does DNA pol I do?
prokaryotic

degrades RNA primer and fills gap with DNA
What does DNA ligase do?
seals link between Okazaki fragments
Where does telomerase add DNA?
the 3' end of chromosomes
What is the end replication problem?
The last RNA primer on the end of the lagging strand can't be converted to DNA, so it is degraded and the new chromosome is shorter
How does nucleotide excision repair work?
endonucleases release oligonucleotide with damaged bases

DNA pol and ligase fill and reseal the gap
What causes xeroderma pigmentosum?
mutation hampers nucleotide excision repair

thymidine dimers cannot be repaired after UV light exposure
How does base excision repair work?
glycosylases recognize and remove damaged bases

AP endonuclease cuts at apyrimidinic site

empty sugar is removed and gap is filled and resealed
What is base excision repair important for?
spontaneous/toxic deamination
How does mismatch repair work?
unmethylated daughter strand is recognized

mismatched nucleotides are removed

gap is filled and resealed
What causes HNPCC?
a mutation hampering mismatch repair
How does nonhomogynous end joining work?
joins 2 ends of dsDNA framents
homology is not required
What causes ataxia telangiectasia?
a mutation preventing nonhomologous end joining
What are the features of ataxia telangiectasia?
ataxia
telangectasias
X-ray hypersensitivity
lymphomas
Why is DNA synthesized 5' to 3'?
Incoming 5' bears the triphosphate bond (energy source for the reaction) that is attacked by the 3' OH group
What is the direction of protein synthesis?
N to C
What are the mRNA start codons?
AUG (and rarely GUG)
How is the starting methionine different in prokaryotes?
It's formyl-methionine (f-Met)
What are the 3 stop codons?
UGA (U Go Away)
UAA (U Are Away)
UAG (U Are Gone...betch)
Where are CAAT and TATA boxes located?
In the promotoer
What occurs at the promoter?
RNA pol and transcription factors bind
What does RNA pol I do?
Makes rRNA
What does RNA pol II do?
Makes mRNA; opens DNA at the promoter site
What does RNA pol III do?
Makes tRNA
What does alpha-amanitin (from death-cap mushrooms) do?
Inhibits RNA pol II --> liver failure
How is RNA processed before leaving the nucleus? ( 3 steps)
Capping of 5'end

Polyadenylation of 3' end

Splicing
What is added to the 5' end of mRNA in the cytosol?
7-methylguanosine
What is the polyadenylation signal?
AAUAA
What is unique about poly-A polymerase?
It doesn't require a template
How is pre-mRNA spliced?
The transcript combines with snRNPs --> spliceosome

Lariat intermediate generated and released
What RNA processing proteins do patients with lupus make antibodies to?
snRNPs
How does the Lac operon repressor work?
The repressor is bound to the operator by default

Lactose binds and inhibits it, allowing expression of lactase
How is the Lac operon promoted?
Catabolite activator protein (CAP) upregulated by cAMP binds its site and helps RNA pol bind the promoter

Glucose inhibits cAMP and the CAP
What nucleotide sequence is present at the 3' end of all tRNAs?
CCA - Can Carry Amino acids
How do tetracyclines work?
Bind 30S rRNA subunit and inhibit the attachment of aminoacyl-tRNA
What are the eukaryotic ribosomal subunits?
40S + 60S --> 80S

Eukaryotic = EVEN
What are the prokaryotic ribisomal subunits?
30S + 50S --> 70S

ODD
What does ATP do to tRNA?
ATP is Activation
What does GTP do to tRNA?
GTP Grips and Goes (translocates)
What occurs at each ribosomal site during protein synthesis?
A: receives all AA-tRNAs (except for initiatory methionine)

P: hold the growing Peptide

E: the Exit site for tRNA
How do aminoglycosides work?
Bind 30S and inhibit initiation complex formation

Cause mRNA misreads
How does chloramphenicol work?
Inhibits 50S peptidyltransferase and peptide bond formation
How do macrolides work?
They block translocation of peptidyl RNA to the P site
How does clindamycin work?
Inhibits peptide bond formation
What does ubiquitin do?
Binds defective proteins, tagging them for proteosomal degradation