central dogma of genetics DNA replication transcription and protein translation

1. WELCOME
TOPIC:- CENTRAL DOGMA OF BIOLOGY.

2. INTRODUCTION
“The central dogma of molecular biology deals with the detailed
residue-by-residue transfer of sequential information. It states that
such information cannot be transferred back from protein to either
protein or nucleic acid.”
Francis Crick, 1958

3. • Protein information cannot flow
back to nucleic acids
• Fundamental framework to
understanding the transfer of
sequence information between
biopolymers

4. The central dogma of biology is that information
stored in DNA is transferred to RNA molecules during
transcription and to proteins during translation.
DNA RNA proteins
Genotyping Phenotyping
RNA DNA/RNA proteins
virus

5. FOUR REQUIREMENTS FOR DNA TO
BE GENETIC MATERIAL
Must carry information
• Cracking the genetic code
Must replicate
• DNA replication
Must allow for information to change
• Mutation
Must govern the expression of the phenotype
• Gene function

6. DNA REPLICATION
Process of duplication of the entire genome prior to cell
division
Biological significance
• extreme accuracy of DNA replication is necessary in
order to preserve the integrity of the genome in
successive generations
• In eukaryotes , replication only occurs during the S
phase of the cell cycle.
• Replication rate in eukaryotes is slower resulting in a
higher fidelity/accuracy of replication in eukaryotes

7. BASIC RULES OF REPLICATION
A. Semi-conservative
B. Starts at the ‘origin’
C. Synthesis always in the 5-3’ direction
D. Can be uni or bidirectional
E. Semi-discontinuous
F. RNA primers required

8. DNA REPLICATION
3 POSSIBLE
MODELS

9. Semi-conservative
replication:
One strand of duplex
passed on unchanged to
each of the daughter
cells. This 'conserved'
strand acts as a template
for the synthesis of a
new, complementary
strand by the enzyme
DNA polymerase

10. HOW DO WE KNOW THAT DNA REPLICATION IS
SEMICONSERVATIVE?
MESELSON-STAHL EXPERIMENTS

11. B) STARTS AT ORIGIN
Initiator proteins identify specific base sequences on DNA
called sites of origin
Prokaryotes – single origin site E.g E.coli - oriC
Eukaryotes – multiple sites of origin (replicator)
E.g. yeast - ARS (autonomously replicating sequences)
Prokaryotes Eukaryotes

12. In what direction does DNA replication occur?
Where does energy for addition
of nucleotide come from?
What happens if a base
mismatch occurs?
C) Synthesis is ALWAYS in the 5’-3’ direction

13. Why does DNA replication only occur in the 5’ to 3’ direction?
Should be PPP here

14. D) UNI OR BIDIRECTIONAL
Replication forks move in one or opposite directions

15. E) SEMI-DISCONTINUOUS REPLICATION
Anti parallel strands replicated simultaneously
Leading strand synthesis continuously in 5’– 3’
Lagging strand synthesis in fragments in 5’-3’

16. SEMI-DISCONTINUOUS REPLICATION
New strand synthesis always in the 5’-3’ direction

17. F) RNA PRIMERS REQUIRED

18. Core proteins at the replication fork
Topoisomerases
Helicases
Primase
Single strand
binding proteins
DNA polymerase
Tethering protein
DNA ligase
- Prevents torsion by DNA breaks
- separates 2 strands
- RNA primer synthesis
- prevent reannealing
of single strands
- synthesis of new strand
- stabilises polymerase
- seals nick via phosphodiester linkage

19. THE MECHANISM OF DNA REPLICATION
Arthur Kornberg, a Nobel prize winner and other
biochemists deduced steps of replication
• Initiation
• Proteins bind to DNA and open up double helix
• Prepare DNA for complementary base pairing
• Elongation
• Proteins connect the correct sequences of
nucleotides into a continuous new strand of DNA
• Termination
• Proteins release the replication complex

20. CORE PROTEINS AT THE REPLICATION FORK

21. 21
PROOFREADING NEW DNA
• DNA polymerase initially makes about 1 in
10,000 base pairing errors
• Enzymes proofread and correct these mistakes
• The new error rate for DNA that has been
proofread is 1 in 1 billion base pairing errors

22. 22
DNA DAMAGE & REPAIR
• Chemicals & ultraviolet radiation damage the
DNA in our body cells
• Cells must continuously repair DAMAGED
DNA
• Excision repair occurs when any of over 50
repair enzymes remove damaged parts of DNA
• DNA polymerase and DNA ligase replace and
bond the new nucleotides together

23. TRANSCRIPTION
• Process of copying DNA to RNA
• Differs from DNA synthesis in that only one strand of DNA,
the template strand, is used to make mRNA
• Does not need a primer to start
• Can involve multiple RNA polymerases
• Divided into 3 stages
• Initiation
• Elongation
• Termination

24. GENERAL FEATURES OF RNA SYNTHESIS
• Similar to DNA Synthesis except
• The precursors are ribonucleoside triphosphates.
• Only one strand of DNA is used as a template.
• RNA chains can be initiated de novo (no primer
required).
• The RNA molecule will be complementary to the DNA
template (antisense) strand and identical (except that
uridine replaces thymidine) to the DNA non-template
(sense) strand.
• RNA synthesis is catalyzed by RNA polymerases and
proceeds in the 5’ 3’ direction.© JOHN WILEY & SONS, INC.

28. TRANSCRIPTION: THE FINAL PRODUCT

29. TYPES OF RNA MOLECULES
• Messenger RNAs (mRNAs)—intermediates that
carry genetic information from DNA to the
ribosomes.
• Transfer RNAs (tRNAs)—adaptors between
amino acids and the codons in mRNA.
• Ribosomal RNAs (rRNAs)—structural and
catalytic components of ribosomes.

30. TRANSLATION
• Components required for translation:
• mRNA
• Ribosomes
• tRNA
• Aminoacyl tRNA synthetases
• Initiation, elongation and termination factors

31. TRANSLATION: INITIATION
• Ribosome small subunit binds to mRNA
• Charged tRNA anticodon forms base pairs with the mRNA codon
• Small subunit interacts with initiation factors and special initiator
tRNA that is charged with methionine
• mRNA-small subunit-tRNA complex recruits the large subunit
• Eukaryotic and prokaryotic initiation differ slightly

32. TRANSLATION: INITIATION
•The large subunit of the ribosome contains three binding sites
•Amino acyl (A site)
•Peptidyl (P site)
•Exit (E site)
•At initiation,
•The tRNAfMet occupies the P site
•A second, charged tRNA complementary to the next codon
binds the A site.

33. TRANSLATION: ELONGATION
• Elongation
• Ribosome translocates by three bases after peptide bond formed
• New charged tRNA aligns in the A site
• Peptide bond between amino acids in A and P sites is formed
• Ribosome translocates by three more bases
• The uncharged tRNA in the A site is moved to the E site.

34. TRANSLATION: ELONGATION
• EF-Tu recruits charged tRNA to A site. Requires hydrolysis of
GTP
• Peptidyl transferase catalyzes peptide bond formation (bond
between aa and tRNA in the P site converted to peptide bond
between the two amino acids)
• Peptide bond formation requires RNA and may be a ribozyme-
catalyzed reaction

35. TRANSLATION: TERMINATION
• Termination
• Elongation proceeds until STOP codon reached
UAA, UAG, UGA
• No tRNA normally exists that can form base pairing with a STOP
codon; recognized by a release factor
• tRNA charged with last amino acid will remain at P site
• Release factors cleave the amino acid from the tRNA
• Ribosome subunits dissociate from each other
• Review the animation of translation

37. REFRENCES:-
• Life sciences, fundamentals and practices-2,pranav
kumar and usha mina,5th edition,2016.
• Slideshare.com
• http://www.thelifewire.com

38. Thank you….