DNA Structure Flashcards
What is Rett Syndrome?
A genetic disorder that causes defects in the methyl-CpG-binding protein 2 involved in chromatin conformation.
Neurodevelopment disorder that only affects females, lethal in males.
What is the central dogma?
Flow of information from DNA to RNA and eventually to proteins
What type of covalent bond joins deoxyribonucleotides?
3’,5’-phosphodiester bonds
What is the primary structure of DNA?
Covalent makeup and base pair sequence
What is the secondary structure of DNA?
Stable structure taken up by some or all of the nucleotides.
I.e. double helix
What is the tertiary structure of DNA?
Complex folding of eukaryotic chromatin and bacterial nucleoids to form large chromosomes.
What are some features of the DNA molecules?
- Joined by 3’,5’-phosphodiester bonds
- Each strand has a 5’ and 3’ end, and thus polarity
- the two strands are antiparallel
- the two strands are complementary
What are Chargaff’s Rules?
Adenosine=thymine and guanosine=cytidine
Purines=Pyrimidines
Species have different base compositions
What are four characteristics of the DNA double helix?
- Two strands coiled around the axis of symmetry.
- antiparallel
- Hydrophilic backbone on outside, hydrophobic bases on the inside.
- Major and minor grooves
What is Actinomycin D?
Anti cancer drug that intercalates between the planar bases
What is B-DNA?
Right-handed double helix.
Hydrophilic backbone on outside, bases on the inside.
10 bp/turn
Most common form of DNA in nature
What is Z-DNA?
Rare left-handed double helical form of DNA
Occurs in G-C rich sequences
May be related to gene regulation
What is A-DNA?
Right-handed helix produced by dehydrating the B form.
11 bp/turn and planes are tilted away from the perpendicular to the axis
Conformation found in DNA-RNA hybrids or RNA-RNA double-stranded regions
What is the importance of denaturing DNA molecules?
Allows access to encoded information.
What causes DNA denaturation?
Heat
-pH extremes
Urea
Other denaturing agents
What is the hyperchromic effect?
Absorbance to UV light goes up as DNA becomes denatured (more single-stranded)
What causes the Tm of a region of DNA to be higher or lower and why?
The amount of GC base pairs in the region, due to GC having 3 H-bonds instead of 2.
More GC = higher Tm
How is DNA packaged in viruses?
Genome surrounded by a protein coat
How is DNA packaged in bacteria?
A single circular chromosome housed in their nucleoid and smaller circular plasmids that often have no function, but can give antibiotic resistance.
How is DNA packaged in eukaryotes?
Packaged into chromatin
What is chromatin?
The complex of nucleic acids (DNA and RNA) and proteins (histones and nonhistones) comprising eukaryotic chromosomes
What is the difference between Euchromatin and heterochromatin?
Euchromatin - loosely packaged and transcriptionally active, beads on a string DNA
Heterochromatin - tightly packaged and transcriptionally inactive
What are histones?
DNA-binding proteins that contain large amounts of basic amino acids (positively charged) such as lysine and arginine which attract negatively charged DNA.
What are nucleosomes?
The structural unit for packaging chromatin consisting of a DNA strand around a histone core.
What is the histone core of a nucleosome comprised of?
Two copies of histones H2A, H2B, H3, and H4.
What is the role of histone H1?
Associated with linker DNA found between nucleosomes to help package chromatin into higher order structures that eventually form chromosomes.
What is positive supercoiling?
Winding the DNA duplex in the same direction as that of the turns of the double helix.
What is negative supercoiling?
Twisting the duplex DNA molecule in a direction opposite to the turns of the strands of the double helix.
What is the biological significance of supercoiling?
Maintaining a negatively supercoiled state allows easier separation of the strands for processes such as replication and transcription.
What is the function of topoisomerases?
Relax supercoiling stress and maintain negative supercoiling by breaking DNA and resealing the breaks
What is the target of ciprofloxacin (a quinolone) and doxorubicin (anti cancer)?
Topoisomerases
What are the three structures in chromosomes necessary for propagation?
Centromere
Telomere
Origin of replication
What is a Centromere?
Region of a chromosome to which spindle tration fibers attach during mitosis and meiosis
What is a telomere?
A specialized repeated DNA sequence, along with specialized proteins, found at the ends of chromosomes.
Shortening of telomeres provides a mitotic clock
What is an origin of replication in a chromosome?
Nucleotide sequence at which DNA synthesis begins.
Spaced about every 50,000 bp in humans.
What is a karyotype and what is it in humans?
Chromosomal complement of a cell
23 pairs of chromosomes in humans.
What are epigenetic modifications?
Non-sequence based changes to DNA that are propagatable through mitosis or meiosis.
What are the two mechanisms for DNA methylation?
- sterically inhibiting the binding of trans-acting factors, repressing transcription, but sometimes can activate if factors are repressive.
- serving as a recognition motif for binding of specific factors.
What catalyzes DNA methylation?
DNA methyltransferases, using S-adenosyl methionine (SAMe) as the donor.
What is removal of DNA methylation catalyzed by?
Ten-eleven translocation enzymes (TET)
Thymine-DNA glycosylase (TDG)
-removes thymine moieties from G/T mismatches
How does histone acetylation occur?
Transfer of an acetyl group from acetyl CoA to the e-amino group of a lysine residue
Causes partial neutralization of the positive charge of histones.
What are 6 forms of histone modifications?
Acetylation
Methylation
Phosphorylation
ADP-ribosylation
Ubiquitination
Biotinylation
What controls the acetylation of histones?
Histone aceytltransferases (HATs)
Histone deacetylases (HDACs)
What are used in treating myelodysplastic and myelodysplastic/myeloproliferative overlap syndromes?
Hypomethylating agents
How is Sezary syndrome treated?
HDAC inhibitors
