1. Lecture:10
The Central Dogma of Molecular Biology
Dr.Q.M.I.Haq

2. The Central Dogma of Molecular Biology
First proposed by Francis Crick (1958)
He said that the sequence involved in the expression of hereditary characteristics is:
The Central Dogma involves three major players, namely DNA, RNA, and proteins.
It also involves three processes, namely DNA replication, transcription, and translation through protein synthesis.
It forms the basis of storage, transmission, and expression of hereditary information.

3. The Central Dogma of Molecular Biology

4. DNA Replication The DNA duplication.
The transfer the genetic information from a parent to a daughter cell.
The DNA base sequences are precisely copied.

5. unwinds part of DNA helix
Replication: 1st step
Unwind DNA
helicase enzyme
unwinds part of DNA helix
stabilized by single-stranded binding proteins
Replication: 2nd step
Build daughter DNA strand
add new complementary bases
DNA polymerase III
Replication
Adding bases
can only add nucleotides to 3 end of a growing DNA strand
need a “starter” nucleotide to bond to
strand only grows 53

6. Leading & Lagging strands
Okazaki
Limits of DNA polymerase III
can only build onto 3 end of existing DNA strand 5
Okazaki fragments 5 5  3 5 3 5 3
ligase
Lagging strand 3
growing
replication fork 3 5
Leading strand 3  5
Lagging strand
Okazaki fragments
joined by ligase
“spot welder” enzyme 3
DNA polymerase III
Leading strand
continuous synthesis

7. Telomeres RNA primer built by primase
serves as starter sequence for DNA polymerase III
DNA polymerase I
removes sections of RNA primer and replaces with DNA nucleotides
Telomeres
Repeating, non-coding sequences at the end of chromosomes = protective cap
Telomerase
enzyme extends telomeres
different level of activity in different cells

8. editing, repair & primer removal
DNA polymerases
Roger Kornberg
2006
DNA polymerase III
1000 bases/second!
main DNA builder
DNA polymerase I
20 bases/second
editing, repair & primer removal
Arthur Kornberg
1959
In 1953, Kornberg was appointed head of the Department of Microbiology in the Washington University School of Medicine in St. Louis. It was here that he isolated DNA polymerase I and showed that life (DNA) can be made in a test tube. In 1959, Kornberg shared the Nobel Prize for Physiology or Medicine with Severo Ochoa — Kornberg for the enzymatic synthesis of DNA, Ochoa for the enzymatic synthesis of RNA.

9. Matthew Meselsson and Franklin Stahl
DNA Replication
(SEMICONSERVATIVE and SEMIDISCONTINOUS)
2 old strands
It is SEMICONSERVATIVE or the 2 old strands will serve as the template for the formation of 2 new strands.
It is SEMIDISCONTINOUS or the new strands formed are attached by fragments (Okazaki fragments).
1 new strand
1 old strand
Matthew Meselsson and Franklin Stahl

10. Example of DNA Replication
5’ TAC CGG AAT GCA ATG CAT ATG 3’ OLD
3’ ATG GCC TTA CGT TAC GTA TAC 5’ OLD
3’ ATG GCC TTA CGT TAC GTA TAC 5’ NEW
5’ TAC CGG AAT GCA ATG CAT ATG 3’ NEW

11. Large team of enzymes coordinates replication
DNA Replication
Large team of enzymes coordinates replication
Enzymes
more than a dozen enzymes & other proteins participate in DNA replication