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103 Cards in this Set
- Front
- Back
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General Structure of chromatin
What makes up the 'beads on a string' |
DNA (negatively charged) loops twice around a histone octamer (positively charged - 2 sets of H2A, H2B, H3, H4) --> bead
Linker histone H1 connects beads --> string "Beads on a string" |
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What is a nucleosome "bead"?
What is it made of? |
2 sets of histone proteins (H2A, H2B, H3, H4) with DNA wrapped around twice
Octamer subunits made of lysine and arginine (pos. charged) |
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What happens to chromatin in mitosis?
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DNA condenses to form mitotic chromosomes
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3 differences between heterchromatin and euchromatin
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HeteroChromatin (Highly Condensed) - condensed, transcriptionally inactive, sterically inaccessible
Euchromatin (truly transcribed) - less condensed, transcriptionally active, sterically accessible |
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Only core protein that is not in the nucleosome core
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H1
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Purines
Structural difference between the two |
Pur As Gold
Purines = Adenine, guanine Guanine has a ketone, Adenine has an amine |
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Pyrmidines
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CUT the Py
Cytosine, uracil, thymine = pyrimidines |
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2 differences between thymine and uracil
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1. THYmine has a meTHYl
2. Thymine found in DNA, Uracil found in RNA |
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How is uracil made?
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deaminate cytosine
NH2 --> ketone group |
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In DNA, which nucleotides bond to each other?
How are the bonds between different pairs different? How does this translate into a physical property? |
G-C, A-T
G-C bonds are stronger because they have 3 H bonds (instead of just 2) More G-C bonds --> higher melting pt. |
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3 amino acids necessary for purine synthesis
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GAG
glycine, aspartate, glutamine |
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Amino acid necessary for pyrimidine synthesis
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aspartate
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What is the difference between a nucleoside and a nucleotide?
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nucleoside = base + ribose
nucleotide = base + ribose + phosphate, linked by a 3'-5' phosphodiester bond |
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Precursor of purines
Precursor of pyrimidines |
Purines = IMP
Pyrimidines = orotate, PRPP added later |
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Enzyme that makes ribonucleotides to deoxyribonucleotides
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ribonucleotide reductase
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2 pathways that use carbamoyl phosphate
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de novo pyrimidine synthesis and urea cycle
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What happens if a person has ornithine transcarbamoylase deficiency (urea cycle)
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Build up of carbamoyl phosphate --> lots of oritic acid, NH3
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Patient has
-lots of oritic acid in the urine -megaloblastic anemia that does NOT improve with vit. B12 or folic acid -failure to thrive 2 things on your differential, and what test would you run to differentiate between the two |
CHECK ammonia
If no hyperammonemia --> orotic acuria (problem in pyrimidine synth) If hyperammonemia, ornithine transcarbamylase deficiency (urea cycle) |
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Pathway for de novo purine synthesis
required amino acids and cofactors? |
Ribose 5-P (from glucose) --> PRPP --> IMP --> AMP and GMP
Need glutamine, aspartate, glycine, and THF |
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De novo pyrimidine synthesis
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Carbamoyl phosphate (from glutamine) + aspartate --> Orotic acid
+ PRPP --> UMP --> UDP --> CTP and dUDP (ribonucleotide reductase) --> dUMP --> dTMP (thymidylate synthase and THF) |
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Patient has
-orotic acid in urine -megaloblastic anemia -NO hyperammonemia -failure to thrive 1. dx 2. dysfunction is where? 3. how is this inherited 4. treat? |
1. Orotic adicuria
2. cannot convert orotic acid to UMP, problem maybe with... -orotic acid phosphoribosyltransferase -orotidine 5'-phosphate decarboxylase 3. autosomal recessive 4. give oral uridine |
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Hydroxyurea
MOA |
inhibits ribonucleotide reductase
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6 mercaptopurine
MOA |
blocks de novo purine synthesis
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5 fluorouracil
MOA |
Inhibits thymidylate synthase --> decrease dTMP
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Methotrexate
MOA |
inhibits dihydrofolate reductase --> decrease dTMP
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Trimethorpim
MOA |
Inhibits bacterial dihydrofolate reductase --> decrease dTMP
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Drug that inhibits dihydrofolate reductase
a. in humans b. in bacteria |
a. methotrexate
b. trimethoprim |
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Role of HGPRT
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converts guanine --> GMP
hypoxanthine --> IMP |
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Role of APRT
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converts adenine --> AMP
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Role of Adenosine deaminase
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Converts adenosine --> inosine
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Role of Xanthine oxidase
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converts hypoxanthine --> xanthine --> uric acid
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Enzyme deficiency that can cause SCID
Pathogenesis |
Adenosine deaminase
enzyme deficiency --> buildup of ATP/dATP --> feedback inhibition of ribonucleotide reductase --> decreased DNA synth --> decreased lymphocyte count |
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Adenosine deaminase deficiency
a. what disease b. who does it affect c. treatment |
a. SCID
b. kids c. experimental human gene therapy |
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Disease associated with HGPRT deficiency
genetics? |
Lesch Nyhan
X-recessive He's Got Purine Recovery Trouble (HGPRT) |
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symptoms:
-retardation -self-mutilation -aggression -hyperuricemia -gout -choreoathetosis dx? pathogenesis |
Lesch Nyhan
deficiency in HGPRT |
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What are 4 important features of the genetic code
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1. unambiguous = each codon --> 1 amino acid
2. Redundant = more than 1 codon may code for the same aa 3. Comma-less/non-overlapping = read from a fixed starting point as a continuous sequence of bases 4. Universal = genetic code is conserved throughout evolution |
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1 exception to the 'degenerate/redundant' property of the genetic code
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Met is only encoded by 1 codon (AUG)
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exception to the non-overlapping property of the genetic code
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some viruses do NOT start at the starting point and read as a continuous sequence of bases
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Exceptions to the 'universal' property of the genetic code
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mitochondria, archaebacteria, mycoplasma, some yeasts
genetic code is not conserved throughout evolution |
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What is a silent mutation
How does it often happen |
mutation in DNA --> same aa
often through base change at 3rd position of a codon (tRNA wobble) |
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What is a missense mutation
conservative? |
missense = mutation that changes the aa
conservative = new aa has similar chemical structure |
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What is a nonsense mutation?
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DNA mutation --> stop codon
STOP this NONsense |
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What is a frameshift mutation
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DNA mutation --> misreading of all nucleotides downstream --> truncated, nonfunctional protein
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Framshift, nonsense, missense
put in order from most to lease severe |
nonsense > missense > silent
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For eukaryotes, where does DNA replication begin
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consensus sequence of base pairs
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DNA replication
This enzyme unwinds DNA template at the replication fork |
helicase
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DNA replication
these prevent DNA strands from reannealing |
Single-stranded binding proteins
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DNA replication
These enzymes create a nick in the helix to relieve supercoils created during replication |
DNA topoisomerase
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This enzyme makes an RNA primer on which DNA pol III can initiate replication
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primase
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This enzyme elongates the leading strand and lagging strand by adding deoxynucleotides to the 3' end
Also has 3'--> 5' exonuclease acitvity (proofreading) what kinds of organisms have this? |
DNA pol III
Prokaryotic ONLY |
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This enzyme degrades RNA primer and fills in the gap with DNA
types of organisms that use this |
DNA pol I
prokaryotes |
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Enzyme that seals DNA
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DNA ligase
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Fluoroquinilones
MOA |
inhibits DNA gyrase (prokaryotic topoisomerase)
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Mechanism by which DNA pol I excises RNA primer
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5' --> 3' exonuclease
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Process of nucleotide excision repair
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Specific endonucleases cut out the oligonucleotide that has damaged bases --> DNA pol and ligase fill in gap
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A child can only play outside at night
They also suffer from dry skin and are prone to skin cancers (melanoma) What condition? Pathogenesis what structures would you expect to see histologically? |
xeroderma pigmentosum
Mutated nucleotide excision repair mechanism --> DNA damage from UV light cannot be fixed thymidine dimers |
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Process of base excision repair
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specific glycosylase removes damaged base --> AP endonuclease cuts DNA at apyrimidinic site --> empty sugar removed --> gap filled and resealed
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Process of mismatch repair
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Daughter strand (with bases misincorporated) is unmethylated, recognized --> mismatched nucleotides removed --> gap filled and resealed
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What process is mutated in hereditary nonpolyposis colorectal cancer
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Mismatch repair
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What is the repair mechanism if there is a double strand break in DNA
Kind that does not require homology |
Non homologous end joining
Brings together 2 ends of DNA fragments |
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What direction does DNA and RNA synthesis take place?
What structures on these ends make this the direction of synthesis? |
5'-->3'
The 3' OH group on one base attacks the 5' triphosphate bond (provides energy) on the next base |
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Certain drugs block DNA replication by causing chain termination
What is one common mechanism by which this occurs |
modified 3' OH end, preventing the addition of the next nucleotide
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In which direction is mRNA read?
protein read? |
5' --> 3'
protein read Nitrogen --> Carbon |
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Types of RNA
a. most abundant b. longest c. smallest |
a. rRNA
b. mRNA c. tRNA Rampant, Massive, Tiny |
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mRNA start codon
what does it code for in eukaryotes? prokaryotes? |
AUG (or rarely GUG)
"AUG inAUGurates protein synth) Euk - codes for Met, may be removed before translation is complete Prok - formyl-methionine (f-Met) |
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mRNA stop codons
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UGA (U Go Away)
UAA (U Are Away) UAG (U Are Gone) |
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What is a promoter region
What does it contain Rich in which nucleic bases? |
site where RNA polymerase and other transcription factors bind to DNA, located upstream from gene locus
sequence with TATA and CAAT boxes AT-rich |
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What commonly happens if the promoter region is mutated
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dramatic decrease in the amount of gene transcribed
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What is an enhancer on DNA
Where is it located |
stretch of DNA that binds transcription factors, alters gene expression
It can be close/far from the gene it affects or even in the introns |
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What is a silencer in DNA
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stretch of DNA where repressors bind
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In eukaryotes, what proteins are responsible for making
a. rRNA b. mRNA c. tRNA |
a. RNA pol I
b. RNA pol II c. RNA pol III Numbered as their products are used in protein synthesis |
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1 Limitations of eukaryotic RNA pol, 1 special capability
Extra functions of RNA pol II |
Limitation = no proofreading
Capability = can initiate chains RNA pol II can open DNA at the promoter site |
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In prokaryotes, what makes rRNA, mRNA, and tRNA
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single multisubunit RNA polymerase
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a-amanitin
a. function b. physiological effect c. where is it found |
a. Inhibits RNA pol II
b. Ingestion --> liver failure c. death cap mushrooms |
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RNA processing
3 steps |
1. capping on 5' end with 7-methylguanosine
2. polyadenylation of 3' end with about 200 A's (signal sequence is AAUAAA) 3. Splice out introns |
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RNA polyadenylation
a. where does it occur b. What enzyme and what is its special feature c. signal sequence |
a. nucleus
b. Poly-A polymeras -- does not require a template c. AAUAAA |
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what is an initial mRNA transcript called?
After it has been capped and tailed? |
Initial = heterogenous nuclear RNA (hnRNA)
Processed = mRNA |
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mRNA splicing in eukaryotes
a. What is found at the 5' splice site b. what is found at the 3' splice site c. Branch point |
5' = GU
3' = AG Branch pt - Adenosine nucleotides |
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what are the 3 steps of mRNA splicing
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1. primary transcript combines with snRPS and other proteins --> spliceosome
2. Loop formed when the branch point A attacks the 5' splice site 3. 3' end of exon 1 attacks 5' end of exon 2, releases loop |
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I have a condition in which I make antibodies to spliceosomal snRNPs
what condition |
Lupus
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what are
a. introns b. exons |
a. INtrons are INtervening, stay IN nucleus
b. EXons are EXpressed, EXit the nucleus |
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What is alternative splicing
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splicing mRNA in different ways (depending on the tissue) to make unique exon combinations, and thus, unique proteins
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What happens in a beta thalessemia mutation
a. biochemically b. physiologically |
a. mutation in HBB gene (chromosome 11) --> b chain of Hb depleted or decreased
b. anemia, possible buildup of toxic intermediates from a-chain excess binding to RBC membranes |
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tRNA structure
a. how many nucleotides b. shape of structure |
a. 75-90 nucleotides
b. cloverleaf form |
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tRNA
a. what can you find at the 3' end b. what can you find opposite the 3' end |
a. CCA + high percentage of chemically modified bases, aa binding site
b. anticodon end |
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enzyme responsible for joining aa with tRNA
a. what does it use b. what are it's functions |
aminoacyl-tRNA (1 per aa)
a. uses ATP b. scrutinizes aa bound to tRNA, hydrolyzes if wrong |
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what is contained in the aa-tRNA bond necessary for protein synthesis
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energy for peptide bond synthesis
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what are 2 mechanisms by which the accuracy for amino acid selection is upheld
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Aminoacyl-tRNA synthetase
Binding of charged tRNA to the right codon |
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What is the result of a mischarged tRNA in protein synthesis
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reads the usual codon, but inserts the WRONG amino acid
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Drug class that binds the 30s subunit of rRNA, prevents the attachment of aminoacyl-tRNA
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Tetracycline
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What is tRNA wobble?
What property of the genetic code allows for this? |
accurate base pairing is only needed for the first 2 nucleotide positions of an mRNA codon, so the third can 'wobble' and still code for the same aa
Degeneracy/redundancy of genetic code |
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Protein synthesis
how is the initiation phase activated? What happens in the initiation phase? When does this phase end |
activated by GTP hydrolysis
inititiation factors (eIFs) assemble 40s + initiatior tRNA (met-tRNA) eIFs are released when mRNA and the ribosomal subunit assemble with the complex |
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Protein synthesis
what are 3 steps of the elongation phase |
1. aminoacyl-tRNA binds to A site (but not initiator Met)
2. rRNA (ribozyme) catalyzes peptide bond formation, moves growing polypeptide to A site 3. ribosome moves one codon over, so peptidyl RNA is now in P site (translocates) |
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Protein synthesis
Termination |
stop codon is recognized by a release factor completed protein is released from ribosome
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Structure of Eukaryotic ribosome
prokaryotic |
Eukaryotes (Even) = 40s + 60s --> 80s
prOkaryotic (Odd) = 30s +50s --> 70s |
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Protein synthesis
a. role of ATP b. role of GTP |
a. tRNA Activation (charging)
b. Translocation (GTP Gripping and Going places) |
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Protein synthesis
3 sites on ribosome and what happens there |
APE
A = incoming Aminoacyl tRNA P = growing Peptide E = holds Empty tRNA as it Exits |
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antibiotics
inhibits formation of the initiation complex and causes a misreading of mRNA |
aminoglycosides
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Antibiotics
inhibits 50s peptidyltransferase |
chloramphenicol and streptogramins
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2 drugs that bind 50s ribosomal subunit, blocking translocation
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macrolides
clindamycin linezolid |
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Post-translational modificatons
What is trimming |
Removal of N- or C-terminal propeptides from zymogens to generate mature proteins
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Post-translational modificatons
3 types of covalent alterations |
phosphorylation, glycosylation, hydroxylation
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Post-translational modificatons
proteosomal degradation |
attach ubiquitin to defective protein --> tag for breakdown
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