NUCLEIC ACIDS
STRUCTURE
Mahalakshmi Panchavati, Ph.D
Presented to students of QVMS GT ACADEMY
5-October-2012
A Brief History of DNA
• 1866 Mendel identifies inheritance factors in
peas
• 1869 Miescher isolates “nuclein” (DNA) from
wounds
• 1910 Levene Described building blocks of
DNA :Phosphate-sugar-bases
The Pentose Sugar
• Deoxy Ribose Ribose
for DNA for RNA
NITROGENOUS BASES
NUCLEOSIDE
• The Nitrogenous base is covalently bondedwith the ribose sugarthrough a N-glycosidiclinkage
N-Glycosidic
bond
NUCLEOSIDE + PHOSPHATE
GROUP=NUCLEOTIDE
Mononucleotide to Dinucleotide
3’
5’
5’
3’
�Asymmetry
to the DNA
chain.
�5’ end has
phosphate
�3’ end has
free –OH
group
�5’AGCT 3’
A Brief History of DNA
• 1866 Gregor Mendel identifies inheritance factors in peas
• 1869 Miescher isolates “nuclein” (DNA) from wounds
• 1910 Levene Described building blocks of DNA )Phosphate-
sugar-bases)
• 1928 Griffith “Transforming factor” that can make avirulent
bacteria virulent
• 1944 Avery,MacLeod,McCarty DNA is the transforming factor
• 1950 Chargaff 1:1 ratio of A:T and G:C in DNA
• 1952 Hershey and Chase Role of DNA in heredity confirmed.
• 1951 Franklin X-ray diffraction photograph of DNA
• 1952 Watson,Crick and Wilkins DNA is a double helix
Chargaff’s Rule
• DNA from any cell of all organisms should
have a 1:1 ratio of pyrimidine and purine
bases i.e amount of guanine is equal to
cytosine and amount of adenine is equal to
thymine
Discovery of the Structure of DNA
• http://www.nature.com/scitable/content/rosalind-franklin-s-x-ray-diffraction-image-6813382
• http://philosophyofscienceportal.blogspot.com/2010/04/rosalind-franklinx-ray-diffraction.html
Watson explaining the discovery of the double helicalstructure of DNA
(http://www.dnatube.com/video/5905/DNA-Basepairing-explanation-by-James-Watson )
Watson explaining the discovery of the
double helical structure of DNA
How does the base pairing happen?
Base pairing is
complementary
Antiparallel Orientation of the 2
strands
• A sequence ofone strand ofDNA is given as:
• 5’TGCA 3’.
• Thecomplementarysequence is:
• 3’ACGT 5’
• DNA sequence:
• 5’TGCA 3’.
• 3’ACGT 5’
Why is DNA double stranded?
• The role of DNA?
• The Blueprint of life
• Carries all genetic informationnecessary for life.
• How is this information stored?
• In the sequence of bases
• Double strandedness protects the bases from enzymatic and chemical damage
• Double strandedness ensures that thereis always a correct copy to compare ifmistakes do happen
Does DNA have a higher order
structure?
• Prokaryotes:Bacterial genome size: 139 kbp to 13,000 kbp ~ avg of 1.3µ
• Size of bacteria: >1µm to several µm
• Average length of a human DNA: 2.0 × 1013 meters
• That is the equivalent of nearly 70 trips from the earth tothe sun and back.
• On the average, a single human chromosome consists ofDNA Molecule that is almost 5 centimeters.
• Size of a human cell: 10-100µm
• Size of the nucleus: average diameter ~ 6 µm
DNA has to be packaged into the
cell.
How does this happen?
• Prokaryotes:
• have circular DNA
• Use HU protein which
is Histone like protein
• Packaged into
supercoiled structures
Eukaryotic DNA Packaging
Eukaryotic DNA Packaging
The Code
• 1966: Nirenberg and Khorana: crack the genetic code
Central Dogma
•DNA→RNA→PROTEIN
RNA and how is it different from DNA
NA DNA RNA
Sugar Deoxy ribose ribose
Bases A,T,G,C A,U,G,C
Strands double mostly
single
location nucleus Nucleus
and
cytoplasm
pH stability At alkaline ↑ Not stable
Stability stable unstable
How does RNA help the reading of
the code?
• Messenger RNA or
mRNA takes the
message of the code
from the nucleus to the
cytoplasm.
• The process by which
it transcribes this code
is transcription
Ribosomal RNA( rRNA) and
transfer RNA (tRNA)
DNA REPLICATION
• Watson and Crick suggested a model of DNA
replication that was proved later by Messelson and
Stahl.
• This is the Semi-Conservative Replication of
DNA.
• New DNA strands are synthesized using the
parent strand as template and because of base pair
complementarity, the progeny DNA molecule has
1 parent strand and 1 new strand.
DNA Replication
• The first objective wouldbe to “unpackage” andunwind the DNA.
• Replication starts at a point called the “origin”
• Enzymes called Helicasesunwind and unzip theDNA.
• Single strand bindingproteins keep the strandssingle. Replication Fork
DNA Replication: synthesis and
elongation
Speed of replication:1000bp/s
Eukaryotes: multiple origin of
replication
• Speed:~
50bp/s
DNA replication:
bibliography
• http://academic.brooklyn.cuny.edu/biology/bio4fv/page/molecular%20biology/DNA-components.html
• http://www.mun.ca/biology/scarr/iGen3_02-08.html
• http://www.articlesbase.com/k-12-education-articles/nucleic-acid-the-molecular-basis-of-inheritance-4144383.html
• http://www.doctortee.com/dsu/tiftickjian/bio100/dna
• http://encyclopedia2.thefreedictionary.com/Nucleotides
• http://en.wikipedia.org/wiki/File:Nucleotides_1.svg
• http://www.nlv.ch/Molbiology/sites/DNA.htm
• http://textbook.s-anand.net/ncert/class-xii/chemistry/14-biomolecules
• http://www.ucl.ac.uk/~sjjgsca/DNApairing.html
• http://www.tokresource.org/tok_classes/biobiobio/biomenu/dna_structure/index.htm
• http://hypertextbook.com/facts/1998/StevenChen.shtml
• http://www.nature.com/scitable/resource?action=showFullImageForTopic&imgSrc=/scitable/content/18847/pierce_11_5_FULL.jpg
• http://www.motifolio.com/1021132.html
• http://bioweb.wku.edu/courses/biol22000/6StructureNA/default.html
• http://bio3400.nicerweb.com/Locked/media/ch12/nucleosomes.html
• http://www.doctortee.com/dsu/tiftickjian/bio100/chromosomes.html
• http://medical-dictionary.thefreedictionary.com/ribosomal+RNA
• http://www.theodora.com/genetics/glossary_t.html
• http://biology.westfield.ma.edu/Biol203/book/export/html/1