Molecular Flashcards
heterochromatin
highly dense
darker on EM
transcriptionally inactive
euchromatin
less condensed
lighter on EM
transcriptionally active
DNA methylation
represses transcription
mutes DNA
histone methylation
reversibly represses DNA transcription, but can activate it depending on methylation location
(mutes DNA)
histone acetylation
relaxes DNA coiling, allowing for transcription
activates DNA
NucleoSide
base + deoxyribose (Sugar)
NucleoTide
base + deoxyribose + phosphaTe
Purine Nucleotides
A
G
amino acids required for purine synthesis
Glycine
Aspartate
Glutamine
Pyrimidine Nucleotides
C
T (DNA)
U (RNA)
Methotrexate (MTX)
inhibit dihydrofolate reductase (decreasing dTMP - deoxythymidine monophosphate)
(disrupts pyrimidine synthesis)
Adenosine deaminase deficiency
ADA is required for degradation of adenosine and deoxyadenosine. In ADA deficiency, increased dATP, leading to toxicity in lymphocytes.
(major cause of SCID)
Lesch-Nyhan syndrome
Defective purine salvage due to absent HGPRT
HGPRT: Hyperuricemia Gout Pissed off (aggression, self-mutilation) Retardation (intellectual disability) DysTonia
Unambiguous genetic code
Each codon specifies only 1 amino acid
Degenerate/redundant genetic code
Most amino acids are coded by multiple codons.
Wobble—codons that differ in 3rd, “wobble” position may code for the same tRNA/amino acid. Specific base pairing is usually only required in the first 2 nucleotide positions of mRNA codon.
Commaless, nonoverlapping genetic code
Read from a fixed starting point as a continuous sequence of bases.
Universal genetic code
Genetic code is conserved throughout evolution.
DNA replication
5′ to 3′ direction
Origin of replication
May be single (prokaryotes) or multiple (eukaryotes).
AT-rich sequences (such as TATA box regions) are found in promoters and origins of replication.
Replication fork
Y-shaped region along DNA template where leading and lagging strands are synthesized.
Helicase
Unwinds DNA template at replication fork.
Single-stranded binding proteins
Prevent strands from reannealing.
DNA topoisomerases
Create a single- or double-stranded break in the helix to add or remove supercoils.
what inhibits eukaryotic topoisomerase I?
Irinotecan/topotecan
what inhibits eukaryotic topoisomerase II?
Etoposide/teniposide
what inhibits prokaryotic topoisomerase II (DNA gyrase) & topoisomerase IV?
Fluoroquinolones
Primase
Makes an RNA primer on which DNA polymerase III can initiate replication.
DNA polymerase III
Prokaryotes only.
Elongates leading strand by adding deoxynucleotides to the 3′ end.
Elongates lagging strand until it reaches primer of preceding fragment.
3′ to 5′ exonuclease activity “proofreads” each added nucleotide.
(5′ to 3′ synthesis and proofreads with 3′ to 5′ exonuclease.)
DNA polymerase I
Prokaryotic only.
Degrades RNA primer; replaces it with DNA.
DNA ligase
Catalyzes the formation of a phosphodiester bond within a strand of double-stranded DNA.
Joins Okazaki fragments.
Telomerase
Eukaryotes only.
An RNA-dependent DNA polymerase that adds DNA to 3′ ends of chromosomes to avoid loss of genetic material with every duplication.
Often dysregulated in cancer cells, allowing unlimited replication.
Mutations in DNA based on severity
silent «_space;missense < nonsense < frameshift.
Silent
Nucleotide substitution but codes for same
(synonymous) amino acid; often base change
in 3rd position of codon (tRNA wobble).
Missense
Nucleotide substitution resulting in changed
amino acid
example: Sickle cell disease
Nonsense
Nucleotide substitution resulting in early stop
codon (UAG, UAA, UGA). Usually results in
nonfunctional protein.
Frameshift
Deletion or insertion of a number of nucleotides
not divisible by 3, resulting in misreading of
all nucleotides downstream.
examples: Duchenne muscular dystrophy, Tay-Sachs disease.
Splice site
Mutation at a splice site p retained intron in the mRNA p protein with impaired or altered function.
Rare cause of cancers, dementia, epilepsy, some
types of β-thalassemia.
Lac operon
when glucose is absent and lactose is available, the lac operon is activated to switch to lactose metabolism.
