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GENERAL BIOLOGY 2 - S.Y. 2022-2023 - St. Basil the Great


MIDTERM : WEEK 3

LESSON 3: CENTRAL DOGMA OF MOLECULAR BIOLOGY

          Good day, Louisian Gems! You learned in the previous modules the different concepts of Genetics and Heredity where the principles of inheritance
were introduced. You learned about the fundamental principles of inheritance according to Mendel and the other non-mendelian principles that explain the
heredity of various traits of organisms. You also practiced predicting genotypes and phenotypes of offspring and created your family pedigree showing the
unique feature in your family for three generations. For this week, you are expected to complete the Written Work I: Synchronous Quiz, where you are to
answer varied questions about the topic for this week.

At the end of the lesson, you must be able to:

show using a diagram the steps in DNA replication and protein synthesis
list the events in DNA Replication and Protein Synthesis
apply the importance of following steps

When you picture protein, you might be thinking of elite bodybuilders with their protein shakes, egg whites, and plain chicken. It is true; all of these
things contain protein. But when we come down to it, proteins are tiny molecules inside cells, and they are required for all structures and functions inside
cells. Without them, our cells could not do their jobs, and we would die. Like the furniture in your house, proteins wear out over time, so our cells are
continuously making new proteins through the process of protein synthesis.

 But how exactly does protein synthesis take place?


Protein synthesis has three main steps: replication, transcription, and translation. Let's look at each step in detail. The central dogma of molecular
biology is the basic underlying principle in genetics. This explains that DNA codes for RNA, which codes for proteins. The process is shown below:
(https://www.google.com.ph/search?q=central+dogma+of+molecular+biology)

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1. DNA Replication

https://www.expii.com/t/dna-replication-steps-diagram-10210

            DNA replication ensures that each cell has the complete set of DNA molecules during cell division. During DNA replication, the DNA molecules
separate into two complementary strands. Both of them can serve as a template for the new strand. DNA replication in prokaryotes is easy because it usually
begins at a single point in the chromosome. However, eukaryotes have a great challenge because DNA replication usually occurs at a hundred sites in the
cell.

          Different enzymes are essential for carrying out DNA replication. These enzymes unzip DNA molecules by breaking down the hydrogen bonds
between base pairs. As the strands of DNA molecules unwind or separate, the original strands serve as a template for attaching complementary bases. For
example, a strand with the bases ACGTTA would produce a complementary strand with the bases TGCAAT. The resulting complementary strand of DNA
molecules is identical to the original strand. Thus, each DNA molecule undergoing replication produces one original and one new strand.

 The next thing we have to do is to shed light on the mystery of the DNA replication steps of the Eukaryotes.

1. The first significant step for DNA Replication is breaking hydrogen bonds between
the bases of the two antiparallel strands. The unwinding of the two strands is the
starting point. The splitting happens in places of the chains which are rich in A-T. There
are only two bonds between Adenine and Thymine (there are three hydrogen bonds
between Cytosine and Guanine). Helicase  is the enzyme that splits the two strands.
The initiation point where the splitting starts is called the "origin of replication." The
structure that is created is known as "Replication Fork."

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2. One of the most critical steps of DNA Replication is the binding of RNA Primase in
the initiation point of the 3'-5' parent chain. RNA Primase can attract RNA nucleotides
which bind to the DNA nucleotides of the 3'-5' strand due to the hydrogen bonds
between the bases. RNA nucleotides are the primers (starters) for the binding of DNA
nucleotides.

3. The elongation process is different for the 5'-3' and 3'-5' templates.

a. 3'-5' Template: The 5'-3' proceeding daughter strand -that uses a 3'-5'
template- is called the leading strandbecause DNA Polymerase can "read" the
template and continuously adds nucleotides (complementary to the nucleotides of
the template, for example, Adenine opposite to Thymine, etc.).

b. 5'-3' Template: The 5'-3' template cannot be "read" by DNA Polymerase. The
replication of this template is complicated, and the new strand is called the
lagging strand. In the lagging strand, the RNA Primase adds more RNA Primers.
DNA polymerase reads the template and lengthens the bursts. The gap between
two RNA primers is called "Okazaki Fragments."

The RNA Primers are necessary for DNA Polymerase to bind Nucleotides to the 3'
end. The daughter strand is elongated with the binding of more DNA nucleotides.

4. In the lagging strand, the DNA Pol I  -exonuclease- reads the fragments and
removes the RNA primers. The gaps are closed with the action of DNA Polymerase
(adds complementary nucleotides to the gaps) and DNA Ligase (adds phosphate in the
remaining gaps of the phosphate-sugar backbone). Each new double helix consists of
one old and one new chain. This is what we call semiconservative replication.

5. The last step of DNA Replication is Termination. This process happens when the
DNA Polymerase reaches the end of the strands. We can easily understand that in the
last section of the lagging strand, when the RNA primer is removed, the DNA
Polymerase can't seal the gap (because there is no primer). So, the end of the parental
strand where the last primer binds aren't replicated. These ends of linear
(chromosomal) DNA consist of noncoding DNA containing repeat sequences called
telomeres. As a result, a part of the telomere is removed in every DNA replication
cycle.
(https://www.nature.com/scitable/topicpage/dna-replication-and-causes-of-mutation-409/)

6. The DNA Replication is not completed before a repair mechanism fixes possible errors caused during the replication. Enzymes like nucleases remove
the wrong nucleotides, and DNA Polymerase fills the gaps.

          Why is there a need to follow established steps and procedures in this process? We know that DNA replication is a genuinely unique biological
phenomenon wherein steps in this process must be accurate to avoid the development of illness. As Dan Poynter said, "Each step you take reveals a new
horizon. To have taken the first step today. Now, I challenge you to take another."

            Consider the countless times that your cells divide to make you who you are—not just during development, but even now, as a fully mature adult.
Then consider that every time a human cell divides and its DNA replicates, it has to copy and transmit the same sequence of 3 billion nucleotides to its
daughter cells. Finally, consider that in life (literally), nothing is perfect. While most DNA replicates with reasonably high fidelity, mistakes do happen, with
polymerase enzymes sometimes inserting the wrong nucleotide or too many or too few nucleotides into a sequence. Fortunately, most of these mistakes are
fixed through various DNA repair processes. Repair enzymes recognize structural imperfections between improperly paired nucleotides, cutting out the
wrong ones and putting the right ones in their place.

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2. Genetic Transcription
 

          Transcription takes place in the nucleus. It uses DNA as a template


to make an RNA (mRNA) molecule. During transcription, a strand of
mRNA is made complementary to a strand of DNA. Transcription takes
place in three steps: initiation, elongation, and termination. The steps are
illustrated in Figure 1.

Step 1: Initiation

            Initiation is the beginning of transcription. It occurs when the


enzyme RNA polymerase binds to a gene region called the promoter. This
signals the DNA to unwind so the enzyme can "read" the bases in one of
the DNA strands. The enzyme is now ready to make an mRNA strand with
a complementary sequence of bases.

Step 2: Elongation

          Elongation is the addition of nucleotides to the mRNA strand. RNA


polymerase reads the unwound DNA strand and builds the mRNA
molecule using complementary base pairs. There is a brief time during
this process when the newly formed RNA is bound to the unwound DNA.
An adenine (A) in the DNA binds to uracil (U) in the RNA during this
process.

Step 3: Termination (https://courses.lumenlearning.com/wm-biology1/chapter/reading-steps-

of-genetic-transcription/)
           Termination is the ending of transcription and occurs when RNA
polymerase crosses a stop (termination) sequence in the gene. The
mRNA strand is complete, and it detaches from DNA.

3. Translation
DNA translation is the term used to describe the process of protein synthesis by ribosomes in the cytoplasm or endoplasmic reticulum.
The genetic information in DNA is used to create messenger RNA (mRNA) by transcription. Single-stranded mRNA then acts as a template during
translation.
Ribosomes facilitate translation in the cytoplasm by inducing the binding of complementary transfer RNA (tRNA) anticodon sequences to the mRNA.
tRNAs carry particular amino acids, which are linked together by the ribosome. In this process, the mRNA is decoded to produce a specific amino acid
chain, known as a polypeptide. Folding the polypeptide creates an active protein that can perform functions within the cell.

Did you know that…..

     Each gene provides instructions for a functional product: a molecule needed to perform a job in the cell. In many cases, the functional product of a gene
is a protein. For example, Mendel's flower color gene provides instructions for a protein that helps make colored molecules (pigments) in flower petals.
https://www.khanacademy.org/science/ap-biology/gene-expression-and-regulation/translation/a/intro-to-gene-expression-central-dogma
     The human body contains around 100,000 different proteins made by the different combinations of 20 amino acids. Approximately 18-20% of the
bodyweight is due to proteins. https://www.medindia.net/health_statistics/health_facts/interesting-protein-facts.htm

Cellular components involved in DNA translation


The key components required for translation are mRNA, tRNA, ribosomes, and aminoacyl tRNA synthetases. These four structures are briefly explained
below:

1. Ribosome. The ribosome is a complex organelle present in the cytoplasm, which serves as the site of action for protein synthesis. It provides the
enzymes needed for peptide bond formation. The nucleotide sequence in mRNA is recognized in triplets, called codons. The ribosome moves along the
single strand mRNA. When a complementary codon sequence belonging to amino acid bearing tRNA bonds with the mRNA, the amino acid is added to the
chain.

2. Messenger RNA (mRNA). mRNA is used to convey information from DNA to the ribosome. It is a single strand molecule complementary to the
DNA template and is generated through transcription. Strands of mRNA are made up of codons, which signify a particular amino acid added to the
polypeptide in a specific order. mRNA must interact with ribosomal RNA (rRNA), the central component of ribosomal machinery that recognizes mRNA's start
and stop codons, and tRNA, which provides the amino acid once bound with a complementary mRNA codon.

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3. Transfer RNA (tRNA). This is a single strand of RNA composed of approximately 80 ribonucleotides. Each tRNA is read as a ribonucleotide
triplet called an anticodon complementary to an mRNA codon. tRNA carries a particular amino acid added to the growing polypeptide chain if complementary
codons bond.

4. Aminoacyl tRNA synthetases. These enzymes link each amino acid to their corresponding tRNA with the help of a two-step process. Each
amino acid has a unique synthetase, and the active site of each enzyme fits only one specific combination of the amino acid and tRNA.

Steps involved in DNA translation


There are three significant steps in translation: initiation, elongation, and termination.

1. Initiation
For translation to begin, the start codon  5'AUG must be recognized. This is a codon specific to the amino acid methionine, nearly always the first
amino acid in a polypeptide chain.
At the 5' cap of mRNA, the small 40s subunit of the ribosome binds. Subsequently, the larger 60s subunit binds to complete the initiation complex.
The next step (elongation) can now commence.

Modified from Chewie [CC BY-SA 3.0], via Wikimedia Commons

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2. Elongation
The ribosome has two tRNA binding sites; the P site, which holds the peptide chain, and the A site, which accepts the tRNA.
While Methionine-tRNA occupies the P site, the aminoacyl-tRNA that is complementary to the next codon binds to the A site, using energy yielded from
the hydrolysis of GTP,
Methionine moves from the P site to the A site to bond to new amino acid there, so the peptide's growth has begun. The tRNA molecule in the P site no
longer has attached amino acid and leaves the ribosome.
The ribosome then translocates along the mRNA molecule to the next codon, again using energy yielded from the hydrolysis of GTP. The growing
peptide lies at the P site, and the A site is open for the binding of the next aminoacyl-tRNA, and the cycle continues. The polypeptide chain is built up
from the N terminal (methionine) to the C terminal (the final amino acid). (https://ib.bioninja.com.au/higher-level/topic-7-nucleic-acids/73-translation/translation-hl.html

3. Termination
 

One of the three stop codons enters the A site. No tRNA molecules bind to these codons, so the peptide and tRNA in the P site become hydrolyzed,
releasing the polypeptide into the cytoplasm.
The small and large subunits of the ribosome dissociate readily for the next round of translation.

(By LadyofHats [Public Doman], via Wikimedia Commons)

In conclusion, Replication, Transcription, and Translation are the three main processes used by all cells to maintain their genetic information and
convert the genetic information encoded in DNA into gene products, which are either RNAs or proteins, depending on the gene. In eukaryotic cells or those
cells with a nucleus, replication and transcription occur within the nucleus while translation takes place outside of the nucleus in the cytoplasm. In prokaryotic
cells or those cells that do not have a nucleus, all three processes occur in the cytoplasm.

The central dogma of molecular biology is the order of the four nucleotide bases or the Base Sequence that allows your DNA to create your whole
being as an organism. The proteins formed in the process are what help decide your body structure. So, a slight change in the order of the bases would
mean a completely different base sequence and an entirely different outcome.

What would be the RNA base pairs for the sequence' 5-AGGTCCG – 3'?

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 For the example given above, the result should be one of the stop codons that end a series of the protein synthesis process. If one of the bases is
incorrectly paired, a different RNA base is produced, thus leading to unwanted results. Protein synthesis is a delicate biological process that is key to growth,
development, and everyday survival. As our cell carefully performs metabolic activities step by step, we should be reminded to keep relevant things in our life
in order. Written in 1 Corinthians 14:40, "But all things should be done decently and in order." the gifts given by God should not be exercised in chaotic ways.
Services conducted to worship Him should also be orderly. Remember that the life we have right now is a gift from the superior being. How we use this gift
should reflect decency and order always.

III. Generalization
 

        The central dogma of molecular biology describes the flow of genetic information in cells from DNA to messenger RNA (mRNA) to protein. It states that
genes specify the sequence of mRNA molecules, which specifies the sequence of proteins. Because the information stored in DNA is so central to cellular
function, the cell keeps the DNA protected and copies it in the form of RNA. An enzyme adds one nucleotide to the mRNA strand for every nucleotide it reads
in the DNA strand. The translation of this information to a protein is more complex because three mRNA nucleotides correspond to one amino acid in the
polypeptide sequence.

          Transcription is creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides
as a complementary language that enzymes can convert back and forth from DNA to RNA.

     The translation is how mRNA is decoded and translated to produce a polypeptide sequence, otherwise known as a protein.

     Crick's Central Dogma of Molecular Genetics states that the sequence involved in regulating hereditary characteristics is from DNA to RNA to proteins.

     The updated Central Dogma involves the following:

As the template, the synthesis of a new complementary DNA strand using an old RNA in some cells is called replication. Transcription is
accomplished by producing a complementary RNA strand using DNA as a template.
The production of DNA using RNA as a template can be accomplished through reverse transcription.
The coded genetic information carried by mRNA is translated through protein synthesis using tRNA

          The following are the three types of RNA in the cell and their functions:

mRNA carries the information from DNA to the ribosomes.


tRNA translates the genetic message carried by the mRNA through protein synthesis.
rRNA forms the structural component of the ribosome, which serves as the site for attachment of mRNA and tRNA and protein synthesis.

         The linear sequence of nucleotides in DNA is complemented by the linear sequence of nucleotides in the RNA, which determines the linear sequence
of amino acids in the protein synthesized.

REFERENCES: 
 Textbooks

 Rea, Maria Angelica D. et al. (2017) General Biology 2 Rex Book Store Inc.

 Biology 2nd edition by Carmelita M. Capco and Gilbert Yang,


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 Modern Biology by Holt, Rinehart, and Winston, Copyright 2002 by A Harcourt Classroom Education Company.

 Online References

 
Protein synthesis lesson plan – educator's reference desk. Educators Reference Desk. (n.d.). https://eduref.org/lessons/science/get0201
 

Amoeba sisters video recap: DNA vs. RNA & protein ...
(n.d.). https://www.amoebasisters.com/uploads/2/1/9/0/21902384/dna_vs_rna_and_protein_synthesis_updated_recap_by_amoeba_sisters.pdf
 

Shroff, S. (n.d.) interesting Protein Facts. MedIndia.


https://www.medindia.net/health_statistics/health_facts/interesting-protein-facts.htm
 

-END OF LESSON-
 
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If you have questions or clarifications, please message me through LMS or messenger. Use the format below: 
 
Greetings:
 
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