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Sadeeqsheshe the central dogma of molecular biology

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THE CENTRAL DOGMA OF MOLECULAR BIOLOGY

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Sadeeqsheshe the central dogma of molecular biology

  1. 1. THE CENTRAL DOGMA OF MOLECULAR BIOLOGY by Sadeeq Sheshe Cancer Genetics Lab, Department of Bioscience, COMSATS Institute of Information Technology, Islamabad
  2. 2.  The central dogma is a concept in molecular biology that attempts to explains the key processes inside the nucleus of the cell  According to this concept, genetic information in DNA is being replicated, later transcribed to RNA and then translated into the protein  It was earlier thought to be an irreversible process, however the concept of reverse transcription proved otherwise Central Dogma
  3. 3.  DNA replication is the process of making new strands of DNA using another DNA as a template  DNA replication is catalyzed by the enzyme, DNA polymerase whose structure is quite different in both prokaryotic and Eukaryotic cells  However, the process is semi-conservative in both prokaryotic and eukaryotic organisms  This means after the replication, each double stranded DNA is made up of one original strand (template) and a newly synthesized strand. DNA Replication
  4. 4. Figure 1
  5. 5.  DNA replication occurs in 5’-3’ direction  This means the hydroxyl (OH) on the 3’ on the starting nucleotide attacks the alpha phosphate on the incoming nucleotide thus establishing a phospho- diester bond  DNA replication does not start de novo but require short strings of RNA oligos called primers  Primers are synthesized by the enzyme primase DNA replication
  6. 6.  DNA replication consists of 3 steps  Initiation, Elongation and Termination  Prokaryotic replication starts at an Origin of replication  These consensus sequences are recognised by the different proteins involved in replication, forming the pre-initiation complex  The double strands unwinds and primers are synthesized Replication
  7. 7.  Certain proteins are assoicated with the replication process  Primase, Helicase, Topoisomerases and SSB proteins  Primase synthesizes primers  Helicase unwinds double stranded DNA  Topoisomerases relieve tensional force generated due to winding  SSB holds single strands together preventing them to fold and form helical structures  Termination is achieved with the bi-directional synthesis converging at a single point called TER Replication
  8. 8. Figure 2
  9. 9.  This is the process of synthesizing an RNA molecule using DNA as template  It is an enzymatic process catalyzed by a DNA dependent RNA polymerase  RNA polymerase is also structurally different in both prokaryotic and eukaryotic cells  Also moves along5’-3’ direction but does not require primer  Question: why RNA polymerase does not require primer and DNA polymerase do? Transcription
  10. 10. Figure : promoter regions
  11. 11.  Just like the replication process, transcription also has 3 steps; Initiation, Elongation and termination  Transcription initiates by recognition of certain sequences on the template Strand called promoter sequences. This are the start point for transcription.  This follows with the assembly of the transcription machinery  And the elongation follows, in 5’-3’ direction, releasing pyrophosphates  The pyrophosphate is hydrolyzed to 2 inorganic phosphates with release of energy  This energy is the driving force for the process, just like in REPLICATION Transcription
  12. 12. Figure
  13. 13. Figure: Elongation
  14. 14.  The termination step is of two types  The rho dependent and rho independent  Rho is a protein that is part of the polymerase transcription complex  It searches for specific sequences and halt the polymease, hence stopping the transcription  While in rho independent termination, the transcriptional machinery including the polymerase recognized certain sequences along the template and stop Transcription
  15. 15.  This is otherwise known as protein synthesis  The information on the DNA that has been transcribed into RNA is finally translated into a protein  The information on the RNA are recognized as codons which are triplets of bases.  Each amino acid has a codon although, one amino acid can have more than one codon  This is degeneracy of the protein code Translation
  16. 16. Figure
  17. 17.  Translation takes place outside the nucleus, specifically on the famous organelle, ribosome  Although, the ribosome has two different structural subunits in both prokaryotic and eukaryotic cells, it is quite structurally distinct in both cells  These sub units together with various proteins that assist in translation form the translational machinery  Each amino acids is first activated by attachment to an Adapter RNA, tRNA catalysed aminoacyl-tRNA synthetases Translation
  18. 18. Figure
  19. 19.  Translation also occurs sequentially in steps: Initiation, elongation and termination  Initiation factors help assemble the machinery and allow the small subunits to search for the start codon, AUG  In prokaryotic cells, the Methionine for the starting AUG is formylated to differentiate from other AUGs in the subsequent parts of the sequence  This distinction is far more complex in eukaryotic cells Translation
  20. 20.  The process continues with the aminoacid-tRNA entering the A site of the ribosome and the used tRNA leaving via the E site  The growing peptide keeps elongating in the P site of the ribosome  The termination is achieved by recognition of the stop codons.  There are 3 stop codons in all organisms Translation
  21. 21.  After translation, the protein is premature  It is modified were it becomes fully functional  This include folding, cleavage, attachment of other groups e.t.c  This is the post translational modification of proteins Translation
  22. 22.  Give at least 3 differences between replication and transcription  Why is synthesis by both DNA and RNA polymerases occur in 5’-3’ direction? Why not in 3’-5’ direction?  What will happen if there is a mistake in replication?  What is the difference between RNA transcript and its DNA template?  What will happen if there is a mistake in translation?  What is the difference between CODON and ANTICODON?  Where does translation takes place? Why does it takes place in that place?  How can you compare and contrast between the 3 process: translation, transcription and replication?  How can you differentiate between prokaryotic and Eukaryotic replication?  Why is replication more complex in Eukaryotes than in prokaryotes? Questions

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