DNA Polymerase and its Conformational Transitions

The abstract of this article explains the conformation transitions in DNA polymerase. DNA polymerase is an enzyme that catalyzes the polymerization of deoxyribonucleotides into a DNA strand. DNA polymerases are best-known for their role in DNA replication, in which the polymerase "reads" an intact DNA strand as a template and uses it to synthesize the new strand. DNA polymerases depend on a series of early steps in the reaction pathway. This allows the selection of the correct nucleotide substrate before the enzyme carries out the chemical step of nucleotide incorporation. The conformational transitions that are involved in these early steps are easily detectable with a variety of fluorescence analysis, which include the fingers-closing transition that has been characterized in structural studies. Scientists have developed a FRET-based assay for the fingers-closing conformational transition that occurs when a binary complex of DNA polymerase I (Klenow fragment) with a primer-template binds a complementary dNTP; they have used this and other fluorescence assays to place the fingers-closing step within the reaction pathway.

Article:

Conformational transitions in DNA polymerase I revealed by single-molecule FRET

Breakdown of DNA in Cancer Cells

This article talks about researchers at the Hebrew University of Jerusalem and how they discovered why cells suffer from insufficient building blocks to support normal DNA replication, during the early stages of cancer development. DNA replication is the process of making an identical copy of a section of duplex (double-stranded) DNA, using existing DNA as a template for the synthesis of new DNA strands.

There is a possibility that cancer development can be ceased by externally supplying the building blocks of DNA. Thus, resulting in reduced DNA damage and significant lower potential of the cells to develop cancerous features. Researchers at the Hebrew University of Jerusalem demonstrated that insufficient levels of the DNA building blocks (nucleotides) required to support normal DNA replication is caused by abnormal activation of cellular generation, which drives many different cancer types. By using laboratory cultures in which cancerous cells were introduced, the researchers were able to show that it is possible to reactivate normal DNA synthesis through external supply of those DNA building block. Thus, opposing the damage caused by the cancerous cells and the cancerous potential it may of caused.

Article:

Researchers Demonstrate Why DNA Breaks Down in Cancer Cells

Chapter 11: Useful Materials

This video describes the structure of DNA and everything involved with it. Nucleotides are the building blocks of DNA (and RNA). Each nucleotide consists of a 5-carbon sugar (deoxyribose), a nitrogen containing base attached to the sugar, and a phosphate group. There are four different types of nucleotides found in DNA, differing only in the nitrogenous base; adenine, guanine, thymine, and cytosine. Adenine and guanine are purines, which are the larger of the two types of bases found in DNA. Cytosine and thymine are pyrimidines; like purines, all pyrimidine ring atoms lie in the same plane. This is just an overview on the structure of DNA. But I thought this video was helpful in knowing the basic components of DNA.

This website (CLICK HERE) provides an animation about DNA replication. I thought this website was quite interesting because it breaks down DNA replication into eight sections to better help you learn. You can also pause, rewind, and fast forward the animation. There are also review questions after each section to check if you retained the knowledge that you just learned. I advise you check out this website!

Cell Adhesion

Cellular adhesion is the binding of a cell to a surface, extracellular matrix or another cell using cell adhesion molecules such as integrins, cadherins, and selectins. Cell adhesion is critical for the genesis and maintenance of both three-dimensional structure and normal function in tissues. Cell adhesion receptors are typically transmembrane glycoproteins that mediate binding to extracellular matrix molecules (ECM) or to counter-receptors on other cells; these molecules determine the specificity of cell-to-cell or cell-to-ECM interaction.

The integrins are cell-surface glycoproteins that act as receptors for ECM proteins, or for membrane-bound counter-receptors on other cells. They also play a role in cell signaling and therefore regulate cellular shape, motility, and the cell cycle. Each integrin is a heterodimer that contains an α and a β subunit with each subunit having a large extracellular domain, a single membrane-spanning region, and in most cases, a short cytoplasmic domain.

The cadherins are a class of type-1, transmembrane proteins. They share an extracellular domain consisting of multiple repeats of a cadherin-specific motif. They play important roles in cell adhesion, ensuring that cells within tissues are bound together. Their name is derived from the fact that they are dependent on calcium (Ca2+) ions to function. This subfamily includes the N-, P-, R-, B-, and E-cadherins, also including 10 other members. These molecules localize in specialized sites of cell-to-cell adhesion that are termed adherence junctions; at these sites cadherins can establish linkages with the actin-containing cytoskeleton.

The selectins are lectin-like adhesion receptors composed of three members, L-, E-, and P-selectin. P-selectin is present in latent form in endothelial cells and platelets; it is rapidly translocated from secretory granules to the cell surface upon cell activation by thrombin or other agonists. E-selectin is synthesized and expressed on endothelial cells in response to inflammatory cytokines such as tumor necrosis factor (TNF) or IL-1. L-selectin is expressed constitutively on leukocytes, but its presentation at the cell surface may be regulated. All selectins are single-chain transmembrane glycoproteins that share similar properties to C-type lectins due to a related amino terminus and calcium-dependent binding.

Article:

Signal Transduction and Signal Modulation by Cell Adhesion Receptors: The Role of Integrins, Cadherins, Immunoglobulin-Cell Adhesion Molecules, and Selectins

Why Does Apoptosis Occur?

This article basically summarizes apoptosis and why it occurs with cells. Apoptosis, or programmed cell death, is a normal component of the development and health of multicellular organisms. Cells die in response to a variety of stimuli and during apoptosis they do so in a controlled, regulated way. In this article, two researchers give their explanations on this topic.

Why are cells that die by programmed cell death generated?

According to Michael Hengartner, senior staff investigator at Cold Spring Harbor Laboratory, "there are several reasons, such as that it gets rid of cells that are not needed, in the way or potentially dangerous to the rest of the organism. Cells that are not needed may never have had a function. In other cases, they may have lost their function, or they may have competed and lost out to other cells. One of the most fascinating reasons for cell death is to get rid of dangerous cells, those that could be harmful to the rest of the organism. Cells could be mutants that would become cancerous; therefore, apoptosis is very important in the formation of cancer. "

H. Robert Horvitz, an expert on apoptosis at the Massachusetts Institute of Technology explains that "the mechanism that generates cells that are needed generates unneeded ones as well (which happens in the immune system); and some cells that die are needed, but only briefly. Cells die either because they are harmful or because it takes less energy to kill them than to maintain them."

Article:

Why does programmed cell death, or apoptosis, occur? Does it take place among bacteria and fungi or only in the cells of higher organisms?

Chapter 9: Useful Materials

This video is an overview of the pathway of signal transduction. Signal transduction pathway is a group of proteins that convert an initial signal to a different signal inside a cell. He explains how signal transduction pathways are used by cells to convert chemical messages to cellular action. Epinephrine is used as a sample messenger to trigger the release of glucose from cells in the liver. The G-Protein, adenylyl cyclase, cAMP, and protein kinases are all used as illustrative examples of signal transduction. He also gives several examples that help you better understand these concepts. Overall, I thought this video was very helpful and was a quick and easy way to help me study!

As I have shared before, Quizlet is a website where you can make flashcards to help you study. I love this website because it really helps when it comes to knowing important terms or definitions. Another thing I like about Quizlet is that you can print out these flashcards to study on the go! You can also quiz yourself and create your own useful flashcards.