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Telomeres, Centromeres, Telomerase, Hererochromatin, Euchromatin, Histones | Molecular Biology

Medicosis Perfectionalis14:04

Transcription

Hey guys, it's Medical Assistant. It's where medicine makes perfect sense. Let's continue our biochemistry discussion. In previous videos, we talked about DNA, RNA, purines, pyrimidines, nucleosides, and nucleotides. Today, let's add the centromere and the telomere.

What does "center" mean? It means center. Look at this, it's exactly in the center. And what does "mere" mean? It means a piece. How about "tilo"? "Tilo" from "tilos" means the purpose or the end. It's the end of the chromosome, this part. And "mere" is another piece. So today, we're talking about the piece in the center and the piece at the end of the chromosome.

Please watch the videos in this playlist in order. When you send an email, what happens? A computer code is generated. Same thing here. If I want my pancreas to make insulin, how do I talk to the pancreas? Send the message via the genetic code. Who has the code? That DNA. The DNA will send the code through RNA, and then the RNA will tell the pancreas to make proteins, such as the famous insulin. Why do we call it insulin? "In" because it's a protein. "Insula" from "insula" means island. What island? Islets of Langerhans, the endocrine islands of the pancreas.

If you forget your name, it's okay. Things happen. However, if you forget the central dogma of DNA, I will be really upset. DNA into another DNA is called replication. Converting DNA into RNA is transcription. The opposite is reverse transcription. RNA to protein is called translation, also known as protein synthesis.

This is the lovely cell, which is the building unit of your body. Inside the cell, there is a lovely nucleus. The nucleus has your DNA, but it's not the only place that has DNA. Other minor structures have it as well. Here is DNA. It's a double helix, mostly right-handed, but it's very long, and your nucleus is so tiny. How come a very long structure fits into a tiny nucleus? Well, if you wrap it around histones gazillion times, eventually, it can occupy a smaller space. When the DNA is wide open like this, it's called euchromatin. "Eu" means true, and "chromatin" from chromosome. Wrap it around histones, wrap it around histones, wrap it around histones, and then it becomes tightly packed, called heterochromatin. Mnemonic: heterochromatin is highly dense, highly condensed. And before you know it, we have the chromosome. The chromosome is the entire thing. Just one of them is a chromatid. So, I have one chromatid and the second chromatid, and between them, there is the central piece known as the centromere.

The different types of histones were discussed before. Just remember that DNA plus histones 2A, 2B, 3, and 4 will give me something called a nucleosome. H1 is also a histone, but it's not part of the nucleosome. Histone one will remain on the outside of the nucleosome, and it helps seal the DNA into the histone while entering or exiting, providing stability. Euchromatin versus heterochromatin. "Eu" is true, "hetero" means different. "Eu" is wide open and relaxed. "Hetero" is very condensed. "Hetero" is highly condensed. Euchromatin is accessible, which means it's transcribable. You can actually work with it. But heterochromatin, well, there is no access. Access is denied. It's transcriptionally silent. Euchromatin appears lighter under a microscope, but "hetero" appears darker because it's highly condensed.

Let's review what we have discussed before. Here is my DNA. It's a double helix. It's anti-parallel. The nitrogenous bases are on the inside, but the sugar-phosphate backbone are to the outside. Never, ever forget that phosphate is at the five prime end, while the hydroxyl is at the three prime. Between the sugar and the phosphate, there is a covalent bond. Between the sugar and the nitrogenous base is also a covalent bond. The famous covalent bond between a nucleotide and the next nucleotide is a three prime, five prime phosphodiester bond. The bonds between the nitrogenous bases are known as hydrogen bonds. Between adenine and thymine, there is a double bond. However, between cytosine and guanine, we have three hydrogen bonds. Since G-C have more hydrogen bonds, the G-C pairing is more stable than A-T. G-C stability. Don't forget, your DNA as a whole is negatively charged, thanks to the negative charge on the phosphate.

Now, to today's topic: centromere. The central piece. Look at that. It's a piece inside my, it's a piece in my chromosome between the two sister chromatids, joining them together. Multimedicosis. If this centromere is capable of joining two sister chromatids together, it means that we have high stability here. Bingo! You know why we have high stability? Because we have high G-C content. High G-C, high stability. The centromere is a site of constriction and indentation. Ever wonder why? Because it's made of heterochromatin, which is highly condensed, highly repetitive sequence. And this can be beneficial. Why is that? Because if even if you degrade a large percentage of it, you did not lose significant information. Because if you lost one, the second one looked exactly like the first one because they are highly repetitive. If I have 20 copies of Gray's Anatomy book in my home and I lost half of them, well, I did not lose any significant information because it's the same book. This centromere will keep those two chromatids together until, until mitosis comes to play. And don't forget that the mitotic spindle will pull this pair here and this pair this way. And before you know it, we have split our centromere, which will help the cell divide, forming two brand new daughter cells. To learn more about this, watch my video titled Mitosis. You will find it in my biology playlist.

Next is one of my favorite topics: telomeres. Telomere means what? The end, or the purpose. Okay, the end. The end piece. Yeah, the end piece of whom? Of the chromosome. Here is what's up: DNA replication, unfortunately, cannot extend all the way until the end of the chromosome. It has to stop and leave the end without replication, which means with each cell cycle of replication, you're losing some of your genetic material which did not replicate. Oh, that's why eventually your telomeres get shorter and shorter and shorter. Look at this. This is a brand new individual, an embryo. But look at this, that's an old guy right here. Too much DNA replication throughout his life. And with each cycle of replication, my telomere gets shortened, increasing my risk of aging. How many courses do we have? Any mechanism in our body to mitigate and ameliorate this problem? Yes, we do. It is called the telomerase, an enzyme that makes telomeres, an enzyme that extends telomeres, so that they do not get shorter or significantly shorter.

A quick note, by the way. The telomeres are at the three prime end. Mnemonic: telomeres are at the three prime end of the chromosome. Who makes the telomeres? Telomerase, which is a reverse transcriptase enzyme. What does that mean? A reverse transcriptase means we'll convert RNA back to DNA. So, bear with me. Telomerase, my hero, is made of two subunits: TERT and TRC. TERT stands for telomerase reverse transcriptase, while TRC stands for telomerase RNA component. We need an RNA component to use it as a template, so that the reverse transcriptase can convert it to DNA. Who is DNA? Your DNA. So that we can keep adding DNA, DNA, DNA to the telomere, so that it does not shorten. Oh, how do you do this? Well, the reverse transcriptase will put DNA, namely TTAGGTTAGGTTAGGT. Why do you keep repeating yourself? Because it's a highly repetitive sequence. What's the good news? If you degrade some of it, I will not lose significant info. Note: This telomerase exists in eukaryotes. However, in prokaryotes, there is no need to make telomeres. Why is that? Because look at this. This is your grandpa. Grandpa can be 90 years old. However, what's the average lifespan of a freaking bacterium? Look it up, and it will blow you away. Bacteria do not need telomerase.

Normally, your cells regenerate. What if I injure myself? Then you're pushing them to regenerate. The more you do it, the more errors are bound to happen. Do it again and again and again. Your telomeres will get shorter. Do it again and again and again. You're getting older. Senescence, aging. What's the function of the telomere? It prevents the loss of DNA material because it's highly repetitive. However, these telomeres, the end of your chromosome, will not replicate. That's why they get shorter with each subsequent division cycle. Who's going to make telomeres and try to prevent or mitigate the shortening? Telomerase, which is an enzyme that synthesizes telomeres. That's why it prevents cell aging by means of reverse transcriptase activity from RNA to DNA. TTAGGT again and again and again.

To understand the profundity of this concept and the significance of telomerase, let's compare between what's going to happen without telomerase and what's going to happen with telomerase. In the absence of telomerase, what's happening? I am shortening my telomeres. Oops. Why? My chromosome is getting shorter and shorter with each cell cycle. That's why these cells at this level are screwed. You're getting older, and if you take it too far, you're toast. Conversely, in the presence of my hero, telomerase, it is preserving the telomeres because it synthesizes them. Your telomeres are not getting significantly shorter, and your cells will grow and grow and grow and grow and grow. Awesome. But if you take it too far, it's neoplasia, which could be benign or malignant.

Once upon a time, Miracosis read the following in a crazy science journal: "In the future, no one would die. Scientists have figured out how to quote prevent aging or quote reverse aging." Well, the devil is in the detail. Give me more detail. Scientists can preserve the telomeres. You know what's going to happen when you preserve your telomeres too much? You're increasing your risk of growth. But if you take it too far, you get what? Cancer. Too little telomerase activity, your telomeres will get shorter, and you'll get senescent. But too much telomerase, yes, they will preserve your telomeres. However, you're increasing your risk of cancer. Demonstrating yet again that there are no solutions in life, only incremental trade-offs. And it doesn't matter how smart you are until you stop and think.

Where does mitosis happen? It happens here, in the M phase of the cell cycle. But how about DNA replication? It happens here, in the S phase, which is part of the interphase. S stands for synthesis of another copy of your DNA. And this DNA replication will be the topic of the next video. But for now, please get a piece of paper and draw the central dogma from scratch.

How does the RNA leave the nucleus and go to the cytoplasm? Through nuclear pores. It's leaving the nucleus and it's going to the cytoplasm. It will be translated in the cytoplasm. Protein synthesis itself will happen in the cytoplasm.

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