Molecular Biology Tutorials

Philadelphia Chromosome and Oncogenic BCR ABL Gene Translocation in CML


Philadelphia Translocation

Philadelphia Chromosome (PH)
(Philadelphia Translocation, PH and Chronic Myeloid Leukemia – CML)

Translocation is a Structural Aberration of Chromosome

Translocation is a type of structural aberration of the chromosome where a segment of chromosome gets translocated to another chromosome. There may be two types of translocation based on the nature of the exchange. They are:

(1). Homologous Translocation

(2). Heterologous Translocation

In homologous translocation, the exchange of chromosomal segments occurs between the homologous chromosomes. In heterologous translocation, the chromosomal segments are exchanged between non-homologous chromosomes. The heterologous translocation in most of the cases will be a reciprocal translocation (exchange of segments between chromosomes).

Translocation causes ‘Position Effect’

The translocation of chromosomes leads to a phenomenon in molecular genetics called the ‘Position Effect’. The position effect is the change in the expression pattern of a gene due to its current position in the chromosome. For example, a normally active gene may be converted to an inactive gene when it is translocated into a new position or vice versa.

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Molecular Biology Tutorials

Extrinsic Pathway of Apoptosis (Apoptosis Molecular Mechanism Part 2)


Receptor Mediated Apoptosis

Extrinsic Pathway of Apoptosis
(The Receptor-Mediated Programmed Cell Death Pathway)

In the extrinsic pathway of apoptosis, the death-inducing signal for the programmed cell death is triggered by an external stimulus. For receiving such an external death-inducing signal, the cell possesses plasma membrane receptors specific to each stimulus and thus the extrinsic signalling of apoptosis is also known as the Receptor Mediated programmed cell death pathway.

The external stimuli for the apoptosis in most of the cases will be a cytokine. The most studied cytokine to induce extrinsic pathway of apoptosis is an extracellular messenger protein called Tumor Necrosis Factor (TNF). TNF is so named because it was first discovered as a protein factor which induces cell death in cancerous cells. The TNF cytokine is produced by the cells of the immune system in response towards the adverse conditions. The adverse conditions that can provoke the immune cells to produce TNF are:

Ø  Exposure to radiation

Ø  Introduction of viral toxins

Ø  Exposure to elevated temperature

Ø  Exposure to other toxic substances

The detailed signaling mechanism of TNF-mediated extrinsic pathway of apoptosis is summarized below:

Ø  TNF first binds to its receptor called TNFR1 (Tumor Necrosis Factor Receptor-1) present on the plasma membrane.

Ø  TNFR1 is a member of death receptor family proteins that turn on the apoptotic cell death process in eukaryotic cells.

Ø  TNFR1 is a trans-membrane receptor with an external ligand binding domain and a cytosolic domain.

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Molecular Biology Tutorials

Apoptosis: The Molecular Mechanism of Programmed Cell Death (Short Notes)


Programmed Cell Death Short Notes

Apoptosis: The Programmed Cell Death

What is Apoptosis? Why apoptosis is known as the ‘Programmed Cell Death’?

The total number of cells in an organ or organism is fundamentally fixed to a specific range in all multicellular organisms. In every multi-cellular organism, the cell number is effectively controlled by two strategies- (a) by regulating cell Division and (b) by regulating cell Death. If cells are no longer needed, they commit suicide (self-destruction) by activating an intracellular death signaling programme. Thus, this death process is known as ‘Programmed Cell Death’. This programmed cell death pathway is called Apoptosis.

The term apoptosis in Greek literally mean ‘falling off’. Just like the old leaves ‘falloff’ from the trees without affecting the life of the plant, the apoptotic cell death will not interfere with the functioning of the organ and organism. The most striking feature of apoptosis is that if a cell undergoes the programmed cell death, the neighboring cells are not at all damaged. Apoptotic death of a cell and its subsequent phagocytosis by a neighboring cell or by a macrophage allow the organic components of the death cell to be effectively recycled.

Learn more: Difference between Apoptosis and Necrosis

The apoptosis is better known as the ‘Programmed Cell Death’. It is a natural well-orchestrated, well sequenced and timely executed chain of events leads to the death of a cell.

What are the characteristics of Apoptotic Cell Death?

An apoptotic cell death is characterized by:

Ø  Shrinkage of the cell

Ø  Shrinkage of the nucleus

Ø  Loss of adhesion to the neighboring cells

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Molecular Biology Tutorials

Different Forms of DNA (A-DNA, B-DNA and Z-DNA) A Comparison Table with PPT


A-DNA, B-DNA and Z-DNA

Different Types of DNA Conformations
(A-DNA, B-DNA and Z-DNA: A Comparison Table)

DNA, the genetic information carrier molecule of the cell, is a long polymer of nucleotides and can adopt different types of structural conformations. The various types of conformations that the DNA can adopt depend on different factors such as:

1.      Hydration level
2.      Salt concentration
3.      DNA sequence
4.      Quantity and direction of super-coiling
5.      Presence of chemically modified bases
6.      Different types of metal ions and its concentrations
7.      Presence of polyamines in solution.

The most common types of structural conformations of DNA are named as:

(1).  A-DNA

(2).  B-DNA

(3).  Z-DNA

Among these three types, the most abundant type of DNA is B-DNA, commonly known as Watson-Crick Model of DNA double helix. The present post describes the structural features of A, B and Z forms of DNA in a comparative manner. We will also discuss the similarities and differences between A-DNA, B-DNA and Z-DNA.

(1). A-DNA

A-DNA is a rare type of structural conformation that a DNA can adopt under dehydrating conditions. A-DNA is a double stranded helical structure almost similar to B-DNA but with a shorter and more compact structural organization. A-DNA was discovered by Rosalind Franklin and the credit for the naming of A-DNA and B-DNA was also accounted to her. Important structural features of A-DNA are given below:

Ø  A-DNA is formed from B-DNA under dehydrating condition.

Ø  A-DNA is much wider and flatter than B-DNA.

Ø  Similar to B-DNA, the A-DNA is also a right handed helix.

Ø  The helix diameter of A-DNA is 26 Å.

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Molecular Biology Tutorials

Difference between Necrosis and Apoptosis: A Comparison Table


necrosis vs apoptosis

Apoptosis vs Necrosis
(Similarities and Differences)

Apoptosis and Necrosis are two types of cell death occur in organisms. The cells undergo death when the cell death becomes necessary as a part of developmental process or they fail to adapt to injuries. Both these types of cell deaths differ in their initial cause and progression of the cell death pathway.

Apoptosis definition (programmed cell death): a physiological process by which unwanted or useless cells are eliminated during the development and other normal biological processes. Often found during tissue homeostasis, embryogenesis, immunological reactions and development of nervous systems. During apoptotic cell death, the cells undergo some characteristic events such as chromatin condensation, nuclear and cytoplasmic aggregation and partitions of cytoplasm and nucleus into membrane bound vesicles called apoptotic bodies containing ribosomes and mitochondria. Apoptotic bodies are recognized and phagocytized by either by macrophages or adjacent cells and thus no inflammatory response are elicited during apoptotic cell death.

Necrosis definition: (accidental cell death) a pathological process occurs when the cells are exposed to serious physical or chemical insults. Occur during pathological infections such as bacterial and fungal infections, hypothermia and hypoxia conditions. The cell and cellular organelles swell and ruptures to release the entire cell content including lysosomal enzymes into the extracellular fluid.  Due to this, necrotic cell deaths are always associated with severe inflammatory response in the surrounding tissues.

The current post describes the similarities and difference between apoptotic and necrotic cell death with a comparison table.

Similarities between Apoptosis and Necrosis

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