-
What type of bond links nucleotides through sugar groups?
phosphodiester bond
-
The 5’ end terminates in a ______group and the 3’ end terminates in a _______group.
phosphate; hydroxyl
-
Chargaff’s rules (4)
- •The base composition of DNA generally
- varies between species.
- •DNA isolated from different tissues of the same organism have the same base composition.
- •Base composition of DNA in a given species does not change with age, nutrition or environment.
- •In all DNAs, regardless of species, the # of A=T and G=C (or # purines = # pyrimidines, A+G = T+C)
-
classic characteristics of DNA structure from the Watson-Crick model (5)
- - right handed double helix
- - has major/minor grooves
- - hydrophilic backbone
- - phosphate backbone is on outside of
- helix
- - hydrophobic bases are inside the helix
-
How RNA is different from DNA (6)
- Thymidine (T) is replaced by Uridine (U)
- Pentose sugar is ribose
- Single-stranded
- complex tertiary structures
- Shorter half-life
- Shorter (in terms of length) than DNA
-
-
limiting factor in cell division
nucleotide synthesis
-
what Glutamine-PRPP amidotransferase is inhibited by (3)
AMP, GMP, IMP
-
During negative feedback regulation of purine
biosynthesis, the ___________ enzyme in the pathway is usually rate-limiting and the ___________.
first; most regulated
-
NMPs are converted to NDPs by ____ nucleoside _____ kinases.
specific; monophosphate
-
NDPs are converted to NTPs by _____ nucleoside _____ kinases.
ubiquitous; diphosphate
-
The cancer chemotherapeutic Gemcitabine is an irreversible inhibitor of _____. This enzyme helps to synthesize deoxyribonucleotides from ribonucleoside diphosphates.
ribonucleotide reductase
-
Chemotherapy drug used to inhibit Thymidylate Synthase?
5-fluorouracil
-
Chemotherapy drugs used to competitively inhibit Dihydrofolate Reductase?
Methotrexate or Aminopterin
(binds w/ 100X higher affinity than dihydrofolate)
-
Purines are degraded by Xanthine Oxidase into
_________?
uric acid
-
Disease in which B and T lymphocytes do not fully develop.
Severe Combined Immunodeficiency Disease (SCID)
-
In Lesch-Nyhan Syndrome, what does the lack of HGPT ultimately result in?
Gout-like tissue damage (due to increased uric acid production)
-
Which DNA Polymerase has 5’ > 3’ exonuclease
activity?
DNA Polymerase I
-
3 stages of DNA replication
- initiation
- elongation
- termination
-
Requires primer to start, helicase unwinds DNA,Topoisomerase II relieves helical tension, stage can be regulated.
initiation
-
DNA Polymerases duplicate the lagging and leading strands.
elongation
-
Termination sequence encountered and stops
replication, Topoisomerase IV unlinks the two intertwined strands.
termination
-
only stage of DNA replication that is regulated
initiation
-
_____________ relieves helical stress caused by unwinding of dsDNA during replication.
topoisomerase II (DNA gyrase)
-
Compared to prokaryotes, eukaryotes have DNA molecules which are (smaller / larger) and are (circular / not circular)
larger; not circular
-
DNA viruses such as Parvovirus, herpes virus pox viruses and HPV undergo _____ replication.
classical semi-conservative
-
Retroviruses involve the +RNA virus being reverse transcribed by _____ specifically known as RNA-dependent DNA polymerase, (RDDP). This produces a RNA/DNA hybrid intermediate.
viral reverse transcription (RT)
-
_____ RNase activity removes the RNA strand while synthesizing a new DNA strand to produce _____.
RT; dsDNA intermediate
-
What must happen before “prodrugs” can become activated?
they must first be phosphorylated
-
3 components of a nucleotide
- nitrogenous base
- pentose (ribose or deoxyribose)
- phosphate
-
nucleoside
nucleotide without a phosphate
-
connects purine/pyrimidine to pentose
 -glycosidic bond
-
effect of cAMP as a secondary messenger
- "fight or flight"
- caffeine effects (inhibits phosphodiesterase)
-
effect of cGMP as a secondary messenger
- vasodilation
- (Viagra inhibits cGMP PDE)
-
part of DNA that is constant
alternative pentose & phosphate backbone
-
part of DNA that is variable
base sequence
-
what the 3' end of DNA terminates in
hydroxyl group
-
what the 5' end of DNA terminates in
phosphate group
-
orientation of 2 strands of DNA
antiparallel
-
type of bonding between base pairs
hydrogen bonding
-
type of RNA that serves as an intermediate in gene expression
mRNA
-
type of RNA that serves as adapters in protein synthesis
tRNA
-
type of RNA that is an integral part of the structure of ribosomes that are involved in protein synthesis
rRNA
-
RNAs that have catalytic activity
ribozymes
-
precursors for de novo nucleotide synthesis (4)
- 1) amino acids
- 2) ribose-5-phosphate
- 3) CO24) NH3
-
when does nucleotide synthesis occur?
during DNA replication
-
nucleic acid purines
adenine; guanine
-
nucleic acid pyrimidines
cytosine, thymine, uracil
-
committed step in de novo purine biosynthesis
PRPP -> 5-phospho- -D-ribosylamine (by glutamine-PRPP amidotransferase)
-
primary regulatory enzyme in de novo pyrimidine synthesis
- aspartate transcarbamoylase (ATCase)
- **1st step
-
inhibits de novo pyrimidine synthesis
CTP (end-product)
-
energy requirement for purine synthesis
6 NTPs
-
energy requirement for pyrimidine synthesis
0-3 ATPs
-
how CTP is formed
amination of UTP
-
2'-2' difluorodeoxycytidine (dFdC)
- Gemcitabine
- cancer chemotherapeutic
- nucleoside analog prodrug
- irreversible inhibitor of ribonucleotide reductase (RNR)
- suicide inhibitor
-
how dUMP is converted to dTMP
methylation by thymidylate synthase
-
result of pyrimidine degradation
ammonia & succinyl-CoA (->CAC)
-
result of purine degradation
uric acid (by xanthine oxidase)
-
xanthine oxidase inhibitor
allopurinol
-
cause of Lesch-Nyhan Syndrome
defect in purine salvage pathway leading to deficiency in HGPT
-
when does mitochondrial DNA replicate?
during cell division
-
principle prokaryotic replication enzyme
DNA Pol III
-
cleanup and repair enzyme in prokaryotes
DNA Pol I
-
how leading strand begins during elongation (in prokaryotes)
DNA primase adds RNA primer
-
prokaryotic enzyme that separates catenated (interlinked circles) DNA
Topoisomerase IV
-
drug with selectivity for prokaryotic topoisomerase II and IV
ciprofloxacin
-
enzyme that links DNA fragments
DNA ligase
-
in eukaryotes, terminate replication and prevent premature shortening of chromosome ends
telomeres
-
eukaryotic polymerase that synthesizes Okazako fragments
DNA Pol
-
eukaryotic polymerase involved in DNA repair
DNA Pol
-
viruses with contain mRNA and can be immediately translated into proteins
postive-strand RNA viruses
-
viruses that must first be converted by RDRP contained within the virion
negative strand RNA viruses
-
viruses that utilize classical semi-conservative replication
DNA viruses
-
viruses that use RNA-dependent DNA polymerase (RDDP) to produce an RNA/DNA hybrid intermediate
retroviruses
-
MOA of AZT against HIV
inhibits reverse transcriptase (RDDP)
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