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