HeteroChromatin - Highly Condensed, inactive, sterically inaccessible.

Euchromatin - less condensed, active, sterically accessible

8 histones.

2 x H2A, H2B, H3, and H4.

PURines: PURe As Gold.

2 rings.

Glycine

Aspartate

Glutamate

Pyrimidines: CUT the PY (pie).

3 rings.

Cytosine deamination makes uricil.

Thymidylate synthase.

Tetrahydrofolate is converted to dihydrofolate.

How do the following antineoplastic and antibiotic compounds interfere with nucleotide synthesis?

Hydroxyurea

6-Mercaptopurine (6-MP)

5-Fluorouracil (5-FU)

Methotrexate (MTX)

Trimethoprim

Hydroxyurea - inhibits ribonucleotide reductase.

6-Mercaptopurine - blocks de novo purine synthesis.

5-Flurouracil - inhibits thymidylate syntase (decreases dTMP).

Methotrexate - inhibits dihydrofolate reductase (decreases dTMP).

Trimethoprim - inhibits bacterial dihydrofolate reductase (decreases dTMP).

What causes orotic aciduria?

What pathway does this involve?

What enzymes are involved?

What is the mode of inheritance?

Inability to convert orotic acid to UMP.

De novo synthesis of pyrimidines.

Defect in orotic acid phosphoribosyltransferase or orotidine 5'-phosphate decarboxylase.

Autosomal recessive.

Increased orotic acid in the urine, megaloblastic anemia, and failure to thrive are clincal features of what disease?

What is the treatment?

Orotic aciduria.

Tx: oral uridine administration.

Severe Combined Immunodeficiency Disease.

What is one of the pathways involved in SCID?

What is the specific enzyme involved?

Purine salvage pathway deficiency.

Adenosine deaminase deficiency.

What is the enzyme deficiency of Lesch-Nyhan syndrome?

What is it's normal function?

What are the results of its deficiency?

What is its mode of inheritance?

HGPRT - defective purine salvage pathway.

Converts hypoxanthine to IMP and guanine to GMP.

Results in excess uric acid production.

X-linked recessive.

He's Got Purine Recovery Trouble.

Findings: retardation, self-mutilation, aggression, hyperuricemia, gout, choreoathetosis.

TransItion - subbing Identical type.

TransVersion - subbing different type; conVersion between types.

1. Unambiguous - each codon specifies one aa.
2. Degenerate/redundant - more than one codon may code for the same aa.
3. Commaless/nonoverlapping - read from fixed starting point as a continuous sequence of bases.
4. Universal - conserved throughout evolution.

1. Silent - same aa.
2. Missense - new aa is similar.
3. Nonsense - early stop codon. "Stop the nonsense"
4. Frame shift - results in misreading.

DNA replication

What is the sequence where DNA replication begins?

DNA replication

At what area are teh leading and lagging strands synthesized?

DNA replication

What enzyme unwinds DNA at the replication fork?

DNA replication

What proteins prevent DNA strands from reannealing?

DNA replication

What enzymes relieve supercoils during replication?

Toposiomerases.

DNA replication

What is the prokaryote specific topoisomerase?

What drug class targets these enzymes?

DNA gyrase.

Fluoroquinolones.

DNA replication

What direction does PolIII have synthesis activity?

Endonuclease activity?

Why does it have endonuclease activity?

5'-3'

3'-5'

Proofreading.

DNA replication

Which prokaryotic polymerase degrades RNA primers and fills in the gaps?

DNA replication

What enzyme seals DNA strands?

1. Nucleotide excision repair
2. Base excision repair
3. Mismatch repair
4. Non-homologous end joining

Two ends of DNA fragments are brought together.

No requirement for homology.

A person cannot repair thymidine dimers.

What disease do they have?

What is the defect?

Xeroderma pigmentosum - dry skin, melanoma, other cancers.

Nucleotide excision repair.

What direction is mRNA read?

What direction is protein synthesized?

5'-3'

N to C

What are the 3 types of RNA?

What is special about each one?

rRNA - most abundant

mRNA - longest

tRNA - smallest

Rampant, Massive, Tiny

What nucleotides are rich in the promotor?

What happens when there is a mutation in the promotor?

AT-rich.

Decreased gene transcription.

Enhancer

Silencer - where repressors bind

Prokaryotes have 1 RNA polymerase.

Eukaryoties have 3 RNA polymeraes - one for each type of RNA.

What compound inhibits RNA PolII and causes liver failure?

Where is it found?

Alpha-amanitin.

Death cap mushrooms.

1. 5' cap
2. Poly-A tail
3. Splicing

1. snRNPs combine with the primary transcript to make the splicosome.
2. Loop is generated.
3. Loop is released joinint 2 exons.

Allows for tRNA wobble.

Different bases in this position can code for the same amino acid.

1. Initiation
2. Elongation
3. Termination

What are the 3 sites of a ribosome?

What occurs at each location?

A site - incoming aminoacyl tRNA.

P site - accommodates growing peptide.

E site - holds empty tRNA as it exits.

1. Aminoacyl-tRNA binds to A site.
2. rRNA catalyzes peptide bond formation; transfers growing polypeptide from A-site.
3. Ribosome advances 3 nucleotides toward the 3' end of RNA, moving the peptidyl RNA to the P-site.

40S + 60S = 80S

Eukaryotes = Even

30S + 50S = 70S

PrOkaryot = Odd

Loading the tRNA into the ribosome (Gripping).

Translocation (Going places).

1. Trimming - removing N- or C-terminal propetides.
2. Covalent alterations - phosphorylation, glycosylation, and hydroxylation.
3. Proteosomal degradation - ubiquitination

1. Phosphorylation
2. Glycosylation
3. Hydroxylation