hey guys it's medical assistant is where medicine makes perfect sense let's continue our biochemistry playlist in previous videos we talked about DNA and RNA we talked about purines versus pyrimidines we talked about nucleosides versus nucleotides and we talked about telomeres and centromeres today it's time to delve into DNA replication how can we replicate your DNA so that we can replicate your cell I.E cell division DNA replication happens here in the S phase of the cell cycle the actual mitosis or division of one cell into two cells happens here at the M or the mitosis phase s for synthesis of DNA M for mitosis please watch the videos in this playlist in order just like the computer code is on the computer the genetic code is on your DNA what's the function to send a message to do what to make proteins like insulin we need to translate that message first from meaningless codons into meaningful proteins and there you go the central dogma when you make another copy of DNA it's called DNA replication this is DNA synthesis which happens in the S phase of the cell cycle DNA 2 RNA is transcription if you go the other way it's reverse transcription and then if RNA becomes protein this is translation also known as protein synthesis before RNA gets translated it needs to exit the nucleus and go to the cytoplasm can DNA exit the nucleus and go to the cytoplasm no because otherwise the DNA will get degraded outside in a second okay why did the RNA leave then why not stay inside because your ribosomes and your endoplasmic reticulum are outside where is my DNA it's in the nucleus mainly but that's not the only site we have some DNA in the mitochondria plants have some DNA in the chloroplast remember that you inherited your DNA from Mommy and from Daddy half and half but you inherited your mitochondrial DNA only from Mommy mnemonic mitochondria is maternal in order for me to work on DNA it needs to be relaxed like this exposed to the enzymes and proteins that will help me replicate my DNA I cannot work on a DNA that is wrapped gazillion times on itself and on histones such as heterochromatin I cannot work with heterochromatin but I can work on the EU chromatin the difference between neochromatin and heterochromatin was discussed in previous videos in a nutshell the euchromatin is relaxed it is accessible which means transcribable people and also replicatable and because it's relaxed it appears lighter under the microscope DNA is the classic anti-parallel structure the nucleotide is made of triple structures what do you mean I mean sugar I mean phosphate and nitrogenous bases complementary base pairing because a binds with T and G binds with C A binding with t requires two hydrogen bond g-binding with C requires three hydrogen bonds that's why the GC is more stable mnemonic JC stability what's the centromere it's the central piece the central piece of what the central piece of your chromosome between the two sister chromatids how come the centromere keeps both sister chromatids connected and linked together because the centromere is made of what heterochromatin highly condensed High really repetitive High JC content JC equals stability so that the two sister chromatids remain connected please understand this the two sister chromatids remain connected throughout the S phase of the cell cycle throughout the process of DNA replication they will split however during the M phase of the cell cycle hashtag mitosis only when the mitotic spindle pulls them apart does the centromere split into two halves or two halves next telomeres Telo means the end or the purpose as in Greek philosophy the T loss and the logos and the Mythos Etc too much Jordan Peterson on this channel did you know that DNA replication cannot extend all the way to the end of the chromosome that's why the end of of the chromosome contains DNA that will not be replicated that's why with each cycle your telomere shortens because it's not replicated so your telomere I.E the end piece of your chromosome will keep getting shorter and shorter and shorter with each subsequent cell division unless you have a telomerase which is a reverse transcriptase enzyme which will make DNA from RNA this DNA will preserve your telomeres or synthesize new ones to be specific I.E the telomerase will prevent the shortening of your telomeres to prevent the loss of genetic material this is awesome two notes notes number one the telomere exists at the three prime end of your DNA only eukaryotes need to synthesize telomere there's a prokaryotes do not because they do not live as long with each cell injury which is followed by cell division trying to regenerate and repair your tissue your telomeres will shorten hashtag senescence you're growing older because of more cell division I.E more shortening of your telomeres but telomerase will save the day in eukaryotes just like you and in the last video we said what's going to happen without telomerase as you see here I'm shortening my telomeres and I'm aging take it too far death but thanks to telomerase I am preserving the telomeres which means my cells will keep dividing and dividing and dividing growing and growing and growing take it too far neoplasia as Dr Thomas Saul said there are no Solutions in life only trade-offs and telomerase is a classic example DNA synthesis I.E DNA replication happens during the S phase of the cell cycle the synthesis phase synthesis of new DNA but the cell division itself dividing of one cell into two separate cells happens during the M phase mitosis during the S phase both sister chromatids remain connected and linked in the middle hashtag centromere but during the M phase the centromere will split hashtag mitotic spindle please pause and review today's topic is DNA replication we are focused on the S phase of the cell cycle please pause and review the central dogma let's replicate your DNA so that we can make it into RNA so that we can secrete proteins why do I need proteins well let me help you with this your insulin is a protein most of your enzymes are proteins all of your receptors are proteins with some carbohydrates all of your channels are proteins all of your pumps including the famous sodium potassium 80 base pump are proteins all of your carriers are proteins the most abundant protein in the blood albumin is a protein and without it you will swell like a welder Beast the second most important protein in your plasma is globulin another bigger protein without it no coagulation factors you will bleed to death no antibodies you will die from infections no transferrin which is a protein that carries iron in the blood oops you get iron problems which can lead to anemia also don't forget that proteins make more than half of your cell membrane you know how many cells do you have like a hundred trillion gazillion something like that let's take that DNA template it and make another template another copy synthesis that's DNA replication occurs in the nucleus let's start I start with my double-stranded DNA the double helix yeah the double helix let's unwind the Helix and open it up who's doing this helicase helicase is the enzyme that will unwind the double helix oh that's a beautiful name and then what I start with the origin of replication and I open some replication forks next the forks will keep forking left and right back and forth up and down these lovely two strands that you had are called parent strands because they are the original strain we will use each of these strands to lay down New Daughter strands why do you call them daughter because they are new they came from the parent who will synthesize the two new daughter strands DNA polymerases okay that's beautiful who's gonna help the polymer races replisome what the flip is that it's a complex of proteins that help with replication oh that makes sense I feel much better let's talk about the difference between bacteria and you both of you have double-stranded DNA however the bacterial DNA is circular in shape but your DNA is linear that's a big difference moreover the bacteria starts one origin of replication but U starts multiple origins of replication even within the same chromosome why because you have more genes because you have more cells because you need more proteins in your life you are a more complex organism who is going to unwind the double helix helicase in both of you who's gonna stabilize the Unwound template strand because listen to me the moment you create the Gap I.E the fork this lovely nucleotides contain nitrogenous species these bases when they are exposed like this not contained but exposed they are very sticky they want to bind to something if they bind to something before you finish they will ruin your DNA replication who's gonna tell them to stop being so sticky single stranded DNA binding proteins they will stick to those exposed bases and tell them to wait until we finish DNA replication since the bacteria have circular DNA I open a fork and before you know it I will keep forking this way and this way but since it's a circle they will meet each other and before you know it we have two DNA molecules instead of one this is a replication however in you as a eukaryote your DNA is linear as you open it up via multiple origins of replication this strand will open up and this one will open up but remember the two sister chromatids remain connected at the center at the centromere as long as we are in the S phase which is the phase of DNA replication later when you go to the m phase mitosis the mitotic spindle will split the centromere into two halves and the S phase DNA synthesis the centromere remains intact both sister chromatids remain connected however when you reach the M phase the mitotic spindle will split your centromere into two halves and therefore the two sister chromatids will separate one will go to each of the two new daughter cells that's the story of my centromere in the S phase it is intact and the two sister chromosome limited remain connected however during the M phase the centromere is split and the sister chromatids are separated one to each new daughter cell who did that mitotic spindle made of what microtubules made of what tibulin protein and just like any other protein it requires DNA replication transcription and translation just to make the tubulin just to undergo mitosis just to replicate your cells your body is amazing two parent strands I already had those however we will use each one as a template to synthesize a new strand so at the end of the day the two parent strands remain but we added two New Daughter strands that's why we say that DNA replication is semi-conservative because we conserved 50 percent from the past and we added 50 percent the two new daughter strains that's why we can call DNA another name we called it negatively charged we called it polar we called it anti-parallel we called it nucleic acid we called it possessing complementary base pairing now let's call it semi-conservative replicator let's review DNA replication occurs in the S phase of the cell cycle let's start with the double-stranded DNA amazing and then start an origin of replication or many because I'm a human being opening those replication forks keep forking this way and this way thank you so much helicase for unwinding the double helix in both directions the moment you open up your DNA those bases are sticky and they want to stick to anything who's gonna protect me from this disaster the answer is a single stranded DNA binding proteins which serve two functions function number one they prevent the newly separated bases from sticking to something else and ruining the DNA replication the second function is that they prevent the destruction of DNA by the nasty nuclease enzyme why do we call it nucleus because it's an enzyme that destroys the nucleus why do I care as a DNA because DNA is in the nucleus doofus that's why it's called nuclease Thank you so these single stranded DNA binding proteins are amazing yeah because they are proteins that bind to the single strand after separation I get it what's the first order of business add a primer what the flip is that short RNA about 10 nucleotides so to speak how can I make this primer which is RNA primase will make it for for you in which direction 5 Prime to three prime just like how DNA polymerase works next my favorite part of the video the super coils here is the story get your lovely headphones the ones with wire not the Bluetooth ones not your earbuds the classic ones from the good old days they are thin and linear according to the science of topology a branch of mathematics if anything is thin and linear torsional pressure will happen that's why the moment you put your headphones in your backpack and come back to retrieve them two days later or so you will find your headphones in Tangled together what the flip I straightened them out before I put them in the backpack I swear I did straighten them out how come they're entangled like this torsional pressure baby topology what do we call is positive super coils okay now what are you going to do with your headphones now well I gotta use them so I will disentangle them how did you do it you did it via adding negative super coils which is a technical term for removing the positive super coils or counteracting the positive super coils so that you disentangle and straighten up your headphone wires again let me take you back to ancient Greece what does time and space mean let's start with time time is called Chrono that's why we talk about chronic diseases diseases that last for a long time how about space space in Greek is toppo so Topo means space yeah because your headphones got entangled in space due to torsional pressure that act upon them in Space by the same flipping token your DNA has double strands it is thin it is long by the laws of nature it should entangle like this if my DNA is entangled like this hashtag positive super coils do you think I'll be able to replicate it no do you think I'll be able to transcribe it no do you think I'll be able to translate it into meaningful proteins also no no proteins no cell division no cell functions you are toast because you're straightened DNA got converted to the evil topoisomer isomer and chemistry means similar yeah it is similar it still contains the same nucleotides and nucleosides everything is there the genetic code is there it just has a different orientation in space rendering it useless so if your DNA got entangled you are finished but hi Miracle says how come I survived all of these years because you have a topoi summer race that will disentangle your DNA I.E prevent it from being entangled in the first place how did it do it and instead of adding positive super coils let's do the opposite add negative super coils I.E prevent the coiling but wait it gets better let's make it clinical do you want to destroy bacteria oh yeah those disease-causing bacteria the bad one of course I want to punch him in the face easy inhibit their topoi summer Race by giving medications that are topoisomerase Inhibitors such as quinolones AG levofloxacin moxifloxacin oxyfloxacin ciprofloxacin and other antibiotics by inhibiting their topoisomerase these bacteria will be left in this state I.E entangled do you think this bacteria can divide no no cell division the bacteria is toast because the life span of the bacterium is very short that's why give the patient a week on those quinolones and boom the pneumonia is gone or the urinary tract infection is gone because without replication the people I mean the bacteria perish this is the beauty of topology microbiology and molecular biology why don't they teach like this in school biochemistry makes so much sense once you understand what the flip you're talking about yet today we have doofuses with stethoscopes running around saying oh why do I need to study molecular biology I will be working in the ICU at the hospital I am not trying to invent a new drug doofus it's because you were work at the ICU at the hospital that you need to learn this because if an organism does not possess to isomerase then giving quinolone antibiotics to them is pointless isn't it to learn more about quinolones and other antibiotics download my antibiotics course at medicosisperfectsnetis.com it will teach you about antibacterials antivirals antifungals and anti-parasitic medications back to DNA replication what should I do to my double-stranded DNA open it up helicase and then what add primers short RNA segments who's going to add them DNA primase We'll add the primers and then what who's going to make the new DNA the daughter strands answer DNA polymerases but please pay attention one of your parents dnas was three prime to five Prime and the other one was five Prime to three prime your DNA polymerase the synthesizer of new DNA only puts no nucleotides in the five Prime two three prime Direction which means it reads from the three prime to five Prime template it will read this template 3 to 5 and synthesize the complementary segment 5 Prime to three prime okay as you see here the helicase is opening it up this way keep opening it up opening it up opening it up and Mr DNA polymerase is adding The New Daughter strand here with a beautiful single stride hashtag leading strand okay but we have a problem on the opposite side this Hiller case will open up your DNA it will Cruise like a sharp knife in warm butter as it cruises it opens up no segments but remember your DNA polymerase only works five Prime to three prime so it will start here and go here and then my helicase will open more so we'll add another segment and it will open more it will add another segment why didn't we do it in a single stride just like the leading strand because the helicase hasn't opened the entire DNA yet so we have to put it in fragments who discovered these fragments a famous Japanese scientist named akazaki that's why we call them okazaki fragments why does Japan has this flag because the Land of the Rising Sun who is gonna bind and ligate and join these okazaki fragments together to make a continuous strand DNA ligase well now let's compare between the leading Strand and the lagging strand the leading strand is continuous one single stride the lagging strand is fragmented the leading strand is comp complementary to the parental 3 Prime to five Prime strand but the lagging strand is complementary to the 5 Prime to three prime parent strand okay leading strand is continuous no need for DNA ligase how about lagging strand it needs DNA ligase I am not saying that the leading strand will never need DNA like this it will need DNA like this as we'll discuss later in the next video on DNA repair when you try to repair a piece of DNA of course you will like it I'm just trying to keep it simple lagging strand of course needs DNA ligase way more than the leading strain leading strand because we started at one point we'll need one primer this is theoretical in reality it needs more than this but we're keeping it simple lagging strand however needs many primers there is a crazy mnemonic that I invented if you may forgive my language I was going to say the lagging strand is is a boot licker but I said let me have some respect for myself and make it an expensive boot Gucci liquor G with the G's and L with the L lagging is a Gucci liquor not just that it's a chattered goatee liquor why because it is dependent on others it's dependent on the DNA ligase it will lick its boot and it's dependent on multiple primers which means multiple primases it will lick their boot now our comparison table is getting longer enzyme needed to make the primer which is RNA in the prokaryotes it's primase in the eukaryotes also primase the enzyme needed to synthesize DNA The New Daughter strands in prokaryotes it's DNA polymerases in eukaryotes DNA polymerases but to which polymerase I am glad you asked if you want to synthesize new DNA which are the daughters strand ends in prokaryotes we're using DNA polymerase 3. in the eukaryotes you're using DNA polymerases Alpha Delta and Epsilon let's add some mnemonic remember that making new DNA means synthesizing no no clear tides and remember the nucleotide is a Triad a trio of sugar nitrogenous base and phosphate so nucleotide three components that's why we have DNA polymerase 3 and we have three different DNA polymerases in humans what are those three DNA polymerases Alpha Delta Epsilon mnemonic add new DNA this Delta you can pronounce it like a d and we are adding no DNA next if you want to remove the RNA primer in either one we're using 5 Prime to 3 Prime exonuclease let me remind you of something remember that we added the primer via primase in the five Prime to three prime Direction so it makes sense to remove it by going in the same direction 5 Prime to 3 Prime exonuclease also remember that the DNA polymerases added DNA in the five Prime to three prime so it all makes sense we always go from the 5 Prime to 3 Prime whether you are making new DNA new primer or removing a primer however this five Prime three prime exonuclease enzyme has different names in prokaryotes and eukaryotes in prokaryotes we call it DNA polymerase one in eukaryotes is the rnas H because it's an enzyme that's removing RNA why do they call it age maybe it's alphabetical but a mnemonic is hella in German means lighter when you make it lighter you're removing stuff I am removing the RNA to make it lighter do you have a mnemonic for the DNA polymerase one yeah easy remember it's always harder to build up than to tear down tearing someone down is easy building up people is different that's why tearing down took just DNA polymerase one but building up requires three that's how I remember it I know it's weird next after removing the primer which is RNA how can I replace this RNA with DNA well DNA polymerase one again and DNA polymerase Delta here how do I remember it Delta in Greek looks like s in English so this is the enzyme that will swap DNA for RNA meaning substitute DNA for RNA IE remove the r RNA throw it in the trash and add DNA instead let's look at it in a different way let's talk about the prokaryotes alone and then the eukaryotes alone first DNA polymerases in prokaryotes we have DNA polymerase one two and three forget two it's not important for your exam just focus on one and three DNA polymerase one it's easier to tear down after you tear down that RNA replaced with DNA oh so it has two functions yes it has two functions in prokaryotes and then you build up with the DNA polymerase 3 synthesizes no DNA amazing we're done next eukaryotes giselian polymerases let's just focus on five these are not the only one there is more Alpha Beta Gamma Delta Epsilon I made a mistake here I should have written them as Alpha Beta Gamma Delta Epsilon I made a mistake I apologize my proofreading mechanisms are are not as robust as my DNA ones more on that in the next video DNA polymerases Alpha Delta and Epsilon will add no DNA IE DNA synthesis DNA polymerases beta and Epsilon will help us repair the DNA which is the topic of the next video DNA polymerase gamma replicates not the nuclear DNA of your nucleus the mitochondrial DNA of your mitochondria remember that you inherited the mitochondrial DNA only from your mother it's purely maternal not paternal mnemonic gamma Gaga Imagine That Lady Gaga is your mama mitochondrial DNA honestly I would rather throw a Viper down my shirt than have Lady Gaga as my mom AZ medicosis chilled down we're done with DNA replication just don't forget that we cannot replicate the last part we cannot extend the replication all the way to the end of the chromosome that's why we have a telomeres without telomerase your telomeres will keep shortening and shorting and shortening and you grow old not just as a person as a cell and the cell that is getting senescent is going to die thankfully you have telomerase as a eukaryote but prokaryotes do not their lifespan is not that long they do not need it anyway and the comparison table is getting longer who's gonna join my okazaki fragments DNA ligase whether it's prokaryotes or eukaryotes who's gonna remove the positive super coils I.E add negative super coils DNA Tuple isomerases next Who's Gonna synthesize the telomeres to prevent the shortening of the telomeres well in eukaryotes is the telomerase in prokaryotes there is nothing it does not apply there so we can write n a here just like Bank of America if you want to be an excellent student bring a piece of paper and draw this table from scratch from memory without looking you're allowed to copy this you can look while copying the point of comparison and do the same thing for this second table from scratch on paper finally some pearls for the pros DNA replication took place in the S phase of the cell cycle cancer is uncontrolled replication of your cells due to errors or mutation chemotherapy is the opposite chemotherapy is trying to treat cancer by inhibiting replication of your DNA some antibacterials and antivirals will try to kill bacteria or kill viruses by inhibiting their DNA not yours to learn more about oncology I.E cancer and the anti-cancer Pharmaceuticals and their mechanisms download my anti-cancer pharmacology course to learn how your beautiful kidneys work download my renal physiology course here is a question for you would you consider the cells of your kidney as labial cells stable cells or quiescent cells let me know the answer in the comment section in the meanwhile Please Subscribe hit the bell and click on the join button you can support me here or here go to my website to download my courses be safe stay happy study hard this is medicosa's perfect status where medicine makes perfect sense