This Khan Academy video explains DNA replication, focusing on the leading and lagging strands. It details the roles of key enzymes like topoisomerase, helicase, DNA primase, and DNA polymerase, and clarifies why replication proceeds differently on each strand due to the 5' to 3' directionality of DNA polymerase.
[{"start_ms":"627","end_ms":"3325","text":"- [Voiceover] Let's talk\na little bit in more depth","start_time_text":"0:00"},{"start_ms":"3326","end_ms":"5805","text":"about how DNA actually copies itself,","start_time_text":"0:03"},{"start_ms":"5805","end_ms":"6845","text":"how it actually replicates,","start_time_text":"0:05"},{"start_ms":"6845","end_ms":"8123","text":"and we're gonna talk about","start_time_text":"0:06"},{"start_ms":"8123","end_ms":"11150","text":"the actual actors in the process.","start_time_text":"0:08"},{"start_ms":"11150","end_ms":"13165","text":"Now, as I talk about\nit, I'm gonna talk a lot","start_time_text":"0:11"},{"start_ms":"13166","end_ms":"17704","text":"about the 3' and 5' ends\nof the DNA molecule,","start_time_text":"0:13"},{"start_ms":"17704","end_ms":"20013","text":"and if that is completely\nunfamiliar to you,","start_time_text":"0:17"},{"start_ms":"20013","end_ms":"22163","text":"I encourage you to watch the video","start_time_text":"0:20"},{"start_ms":"22163","end_ms":"26041","text":"on the antiparallel structure of DNA.","start_time_text":"0:22"},{"start_ms":"26041","end_ms":"28163","text":"And I'll give a little bit\nof a quick review here,","start_time_text":"0:26"},{"start_ms":"28163","end_ms":"31355","text":"just in case you saw it but\nit was a little while ago.","start_time_text":"0:28"},{"start_ms":"31355","end_ms":"33042","text":"This is a zoom-in of DNA,","start_time_text":"0:31"},{"start_ms":"33042","end_ms":"35497","text":"it's actually the zoom-in from that video,","start_time_text":"0:33"},{"start_ms":"35497","end_ms":"37934","text":"and when we talk about the 5' and 3' ends,","start_time_text":"0:35"},{"start_ms":"37934","end_ms":"40848","text":"we're referring to what's\nhappening on the riboses","start_time_text":"0:37"},{"start_ms":"40848","end_ms":"44930","text":"that formed part of this\nphosphate sugar backbone.","start_time_text":"0:40"},{"start_ms":"44930","end_ms":"47051","text":"So we have ribose right over here,","start_time_text":"0:44"},{"start_ms":"47051","end_ms":"48639","text":"five-carbon sugar,","start_time_text":"0:47"},{"start_ms":"48639","end_ms":"50900","text":"and we can number the carbons;","start_time_text":"0:48"},{"start_ms":"50900","end_ms":"54876","text":"this is the 1' carbon,\nthat's the 2' carbon,","start_time_text":"0:50"},{"start_ms":"54876","end_ms":"58516","text":"that's the 3' carbon,\nthat's the 4' carbon,","start_time_text":"0:54"},{"start_ms":"58516","end_ms":"60641","text":"and that's the 5' carbon.","start_time_text":"0:58"},{"start_ms":"60641","end_ms":"62891","text":"So this side of the ladder,","start_time_text":"1:00"},{"start_ms":"64641","end_ms":"65693","text":"you could say,","start_time_text":"1:04"},{"start_ms":"65693","end_ms":"67642","text":"it is going in the ...","start_time_text":"1:05"},{"start_ms":"67642","end_ms":"70526","text":"it is going, let me\ndraw a little line here,","start_time_text":"1:07"},{"start_ms":"70526","end_ms":"73859","text":"this is going in the 3' to 5' direction.","start_time_text":"1:10"},{"start_ms":"75308","end_ms":"79498","text":"So this end is 3' and then this end is 5'.","start_time_text":"1:15"},{"start_ms":"79498","end_ms":"80886","text":"It's going 3' to 5'.","start_time_text":"1:19"},{"start_ms":"80886","end_ms":"83550","text":"Notice three, this phosphate\nconnects to the 3',","start_time_text":"1:20"},{"start_ms":"83550","end_ms":"85934","text":"then we go to the 5'\nconnects to a phosphate,","start_time_text":"1:23"},{"start_ms":"85934","end_ms":"87358","text":"this connects to a 3',","start_time_text":"1:25"},{"start_ms":"87358","end_ms":"88464","text":"then it connects--","start_time_text":"1:27"},{"start_ms":"88464","end_ms":"91463","text":"then we go to the 5'\nconnects to a phosphate.","start_time_text":"1:28"},{"start_ms":"91463","end_ms":"94003","text":"Now on this end, as we\nsaid it's antiparallel.","start_time_text":"1:31"},{"start_ms":"94003","end_ms":"96675","text":"It's parallel, but it's\noriented the other way.","start_time_text":"1:34"},{"start_ms":"96676","end_ms":"99509","text":"So this is the 3', this is the 5',","start_time_text":"1:36"},{"start_ms":"100379","end_ms":"103515","text":"this is the 3', this is the 5'.","start_time_text":"1:40"},{"start_ms":"103515","end_ms":"104979","text":"And so this is just\nwhat we're talking about","start_time_text":"1:43"},{"start_ms":"104979","end_ms":"107562","text":"when we talk about the\nantiparallel structure.","start_time_text":"1:44"},{"start_ms":"107563","end_ms":"109418","text":"These two backbones,","start_time_text":"1:47"},{"start_ms":"109418","end_ms":"111449","text":"these two strands are\nparallel to each other,","start_time_text":"1:49"},{"start_ms":"111449","end_ms":"114660","text":"but they're oriented\nin opposite directions.","start_time_text":"1:51"},{"start_ms":"114661","end_ms":"118833","text":"So this is the 3' end\nand this is the 5' end.","start_time_text":"1:54"},{"start_ms":"118833","end_ms":"120402","text":"And this is gonna be really important","start_time_text":"1:58"},{"start_ms":"120402","end_ms":"122070","text":"for understanding replication,","start_time_text":"2:00"},{"start_ms":"122070","end_ms":"124030","text":"because the DNA polymerase,","start_time_text":"2:02"},{"start_ms":"124030","end_ms":"126767","text":"the things that's adding\nmore and more nucleotides","start_time_text":"2:04"},{"start_ms":"126767","end_ms":"129326","text":"to grow a DNA strand;","start_time_text":"2:06"},{"start_ms":"129327","end_ms":"132827","text":"it can only add nucleotides on the 3' end.","start_time_text":"2:09"},{"start_ms":"133872","end_ms":"136827","text":"So if we were talking\nabout this right over here,","start_time_text":"2:13"},{"start_ms":"136828","end_ms":"138456","text":"we would only be able to add …","start_time_text":"2:16"},{"start_ms":"138456","end_ms":"141741","text":"We would only be able\nto add going that way.","start_time_text":"2:18"},{"start_ms":"141741","end_ms":"144250","text":"We wouldn't be able to add going …","start_time_text":"2:21"},{"start_ms":"144250","end_ms":"147000","text":"We wouldn't be able to add going that way.","start_time_text":"2:24"},{"start_ms":"147000","end_ms":"149386","text":"So one way to think about it\nis you can only add nucleotides","start_time_text":"2:27"},{"start_ms":"149386","end_ms":"153074","text":"on the 3' end or you can only extend …","start_time_text":"2:29"},{"start_ms":"153074","end_ms":"156741","text":"You can only extend DNA\ngoing from 5' to 3'.","start_time_text":"2:33"},{"start_ms":"158793","end_ms":"160978","text":"If you're only adding on the 3' end,","start_time_text":"2:38"},{"start_ms":"160978","end_ms":"165038","text":"then you're going from the\n5' to the 3' direction.","start_time_text":"2:40"},{"start_ms":"165038","end_ms":"167733","text":"You can't go from the\n3' to the 5' direction.","start_time_text":"2:45"},{"start_ms":"167733","end_ms":"172410","text":"You can't continue to add on\nthe 5' side using polymerase.","start_time_text":"2:47"},{"start_ms":"172410","end_ms":"175146","text":"So what am I talking\nabout with polymerase.","start_time_text":"2:52"},{"start_ms":"175146","end_ms":"177045","text":"Well let's look at this\ndiagram right over here","start_time_text":"2:55"},{"start_ms":"177046","end_ms":"178985","text":"that really gives us an overview","start_time_text":"2:57"},{"start_ms":"178985","end_ms":"181023","text":"of all of the different actors.","start_time_text":"2:58"},{"start_ms":"181023","end_ms":"183512","text":"So here is just our of our DNA strand,","start_time_text":"3:01"},{"start_ms":"183512","end_ms":"187269","text":"and it's, you can imagine\nit's somewhat natural,","start_time_text":"3:03"},{"start_ms":"187270","end_ms":"189769","text":"in it's natural unreplicated form,","start_time_text":"3:07"},{"start_ms":"189769","end_ms":"193591","text":"and you could see we've labeled\nhere the 3' and the 5' ends,","start_time_text":"3:09"},{"start_ms":"193591","end_ms":"195436","text":"and you could follow\none of these backbones.","start_time_text":"3:13"},{"start_ms":"195436","end_ms":"199204","text":"This 3', if you follow\nit all the way over here,","start_time_text":"3:15"},{"start_ms":"199204","end_ms":"202914","text":"it goes, this is the corresponding 5' end.","start_time_text":"3:19"},{"start_ms":"202914","end_ms":"206741","text":"So this and this are the same strand,","start_time_text":"3:22"},{"start_ms":"206741","end_ms":"210402","text":"and this one, if you follow it along,","start_time_text":"3:26"},{"start_ms":"210402","end_ms":"212409","text":"if you go all the way over\nhere, it's the same strand.","start_time_text":"3:30"},{"start_ms":"212409","end_ms":"213653","text":"So this is the 3' end,","start_time_text":"3:32"},{"start_ms":"213654","end_ms":"217821","text":"and 3' end of it and then\nthis is the 5' end of it.","start_time_text":"3:33"},{"start_ms":"218954","end_ms":"220118","text":"Now the first thing,","start_time_text":"3:38"},{"start_ms":"220118","end_ms":"221795","text":"and we've talked about\nthis in previous videos","start_time_text":"3:40"},{"start_ms":"221795","end_ms":"224153","text":"where we give an overview of replication,","start_time_text":"3:41"},{"start_ms":"224154","end_ms":"228321","text":"is the general idea is that\nthe two sides of our helix,","start_time_text":"3:44"},{"start_ms":"229992","end_ms":"234031","text":"the two DNA, the double-helix\nneeds to get split,","start_time_text":"3:49"},{"start_ms":"234031","end_ms":"236271","text":"and then we can build another,","start_time_text":"3:54"},{"start_ms":"236271","end_ms":"238756","text":"we can build another side of the ladder","start_time_text":"3:56"},{"start_ms":"238757","end_ms":"241076","text":"on each of those two split ends.","start_time_text":"3:58"},{"start_ms":"241076","end_ms":"244092","text":"You could really view this\nas if this is a zipper,","start_time_text":"4:01"},{"start_ms":"244092","end_ms":"248299","text":"you unzip it and then you put\nnew zippers on either end.","start_time_text":"4:04"},{"start_ms":"248299","end_ms":"250041","text":"But there's a lot of--","start_time_text":"4:08"},{"start_ms":"250041","end_ms":"252419","text":"in reality, it is far more\ncomplex than just saying","start_time_text":"4:10"},{"start_ms":"252419","end_ms":"255300","text":"\"Oh, let's open the zipper\nand put new zippers on it.\"","start_time_text":"4:12"},{"start_ms":"255300","end_ms":"258295","text":"It involves a whole bunch of\nenzymes and all sorts of things","start_time_text":"4:15"},{"start_ms":"258296","end_ms":"260151","text":"and even in this diagram,","start_time_text":"4:18"},{"start_ms":"260151","end_ms":"261845","text":"we're not showing all\nof the different actors,","start_time_text":"4:20"},{"start_ms":"261845","end_ms":"264000","text":"but we're showing you the primary actors,","start_time_text":"4:21"},{"start_ms":"264000","end_ms":"266459","text":"at least the ones that\nyou'll hear discussed","start_time_text":"4:24"},{"start_ms":"266459","end_ms":"270249","text":"when people talk about DNA replication.","start_time_text":"4:26"},{"start_ms":"270249","end_ms":"271576","text":"So the first thing that needs to happen,","start_time_text":"4:30"},{"start_ms":"271576","end_ms":"275483","text":"right over here, it's all\ntightly, tightly wound.","start_time_text":"4:31"},{"start_ms":"275484","end_ms":"276445","text":"So let me write that,","start_time_text":"4:35"},{"start_ms":"276445","end_ms":"278862","text":"it is tightly, tightly wound.","start_time_text":"4:36"},{"start_ms":"280302","end_ms":"281443","text":"And it actually turns out,","start_time_text":"4:40"},{"start_ms":"281443","end_ms":"284052","text":"the more that we unwind it on one side,","start_time_text":"4:41"},{"start_ms":"284052","end_ms":"286421","text":"the more tightly wound\nit gets on this side.","start_time_text":"4:44"},{"start_ms":"286421","end_ms":"288903","text":"So in order for us to unzip the zipper,","start_time_text":"4:46"},{"start_ms":"288903","end_ms":"290584","text":"we need to have an enzyme","start_time_text":"4:48"},{"start_ms":"290584","end_ms":"294861","text":"that helps us unwind\nthis tightly wound helix.","start_time_text":"4:50"},{"start_ms":"294861","end_ms":"298676","text":"And that enzyme is the topoisomerase.","start_time_text":"4:54"},{"start_ms":"298676","end_ms":"300992","text":"And the way that it actually works is","start_time_text":"4:58"},{"start_ms":"300993","end_ms":"304776","text":"it breaks up parts of the\nback bones temporarily,","start_time_text":"5:00"},{"start_ms":"304776","end_ms":"307982","text":"so that it can unwind and\nthen they get back together,","start_time_text":"5:04"},{"start_ms":"307982","end_ms":"311097","text":"but the general high-level\nidea is it unwinds it,","start_time_text":"5:07"},{"start_ms":"311097","end_ms":"312762","text":"so then the helicase enzyme,","start_time_text":"5:11"},{"start_ms":"312762","end_ms":"314044","text":"and the helicase really doesn't look like","start_time_text":"5:12"},{"start_ms":"314044","end_ms":"316351","text":"this little triangle\nthat's cutting things.","start_time_text":"5:14"},{"start_ms":"316351","end_ms":"318057","text":"These things are actually\nfar more fascinating","start_time_text":"5:16"},{"start_ms":"318057","end_ms":"319427","text":"if you were to actually see a--","start_time_text":"5:18"},{"start_ms":"319427","end_ms":"321659","text":"the molecular structure of helicase.","start_time_text":"5:19"},{"start_ms":"321659","end_ms":"323437","text":"But what helicase is doing","start_time_text":"5:21"},{"start_ms":"323437","end_ms":"326874","text":"is it's breaking those\nhydrogen bonds between our …","start_time_text":"5:23"},{"start_ms":"326874","end_ms":"329156","text":"Between our nitrogenous bases,","start_time_text":"5:26"},{"start_ms":"329156","end_ms":"331550","text":"in this case it's an adenine\nhere, this is a thymine","start_time_text":"5:29"},{"start_ms":"331550","end_ms":"335513","text":"and it would break that\nhydrogen bond between these two.","start_time_text":"5:31"},{"start_ms":"335514","end_ms":"337514","text":"So, first you unwind it,","start_time_text":"5:35"},{"start_ms":"339511","end_ms":"340840","text":"then the helicase,","start_time_text":"5:39"},{"start_ms":"340841","end_ms":"342831","text":"the topoisomerase unwinds it,","start_time_text":"5:40"},{"start_ms":"342831","end_ms":"345555","text":"then the helicase breaks them up,","start_time_text":"5:42"},{"start_ms":"345555","end_ms":"347504","text":"and then we actually think about","start_time_text":"5:45"},{"start_ms":"347504","end_ms":"349744","text":"these two strands differently,","start_time_text":"5:47"},{"start_ms":"349744","end_ms":"351108","text":"because as I mentioned,","start_time_text":"5:49"},{"start_ms":"351109","end_ms":"353633","text":"you can only add nucleotides","start_time_text":"5:51"},{"start_ms":"353633","end_ms":"356466","text":"going from the 5' to 3' direction.","start_time_text":"5:53"},{"start_ms":"357693","end_ms":"359863","text":"So this strand on the\nbottom right over here","start_time_text":"5:57"},{"start_ms":"359864","end_ms":"362399","text":"which we will call our leading strand,","start_time_text":"5:59"},{"start_ms":"362399","end_ms":"364236","text":"this one actually has a\npretty straightforward,","start_time_text":"6:02"},{"start_ms":"364236","end_ms":"366427","text":"remember this is the\n5' end right over here,","start_time_text":"6:04"},{"start_ms":"366428","end_ms":"367829","text":"so it can add,","start_time_text":"6:06"},{"start_ms":"367829","end_ms":"370349","text":"it can add going in that direction,","start_time_text":"6:07"},{"start_ms":"370349","end_ms":"373527","text":"it can add going in that\ndirection right over here.","start_time_text":"6:10"},{"start_ms":"373527","end_ms":"375277","text":"This is the 5' to 3',","start_time_text":"6:13"},{"start_ms":"376496","end_ms":"380116","text":"so what needs to happen here\nis to start the process,","start_time_text":"6:16"},{"start_ms":"380116","end_ms":"381949","text":"you need an RNA primer","start_time_text":"6:20"},{"start_ms":"382818","end_ms":"386233","text":"and the character that puts an RNA primer,","start_time_text":"6:22"},{"start_ms":"386234","end_ms":"388107","text":"that is DNA primase.","start_time_text":"6:26"},{"start_ms":"388107","end_ms":"389684","text":"We'll talk a little bit more about","start_time_text":"6:28"},{"start_ms":"389684","end_ms":"391966","text":"these characters up here\nin the lagging strand,","start_time_text":"6:29"},{"start_ms":"391967","end_ms":"393328","text":"but they'll add an RNA,","start_time_text":"6:31"},{"start_ms":"393328","end_ms":"395650","text":"let me do this in a color you can see,","start_time_text":"6:33"},{"start_ms":"395650","end_ms":"397768","text":"an RNA primer will be added here,","start_time_text":"6:35"},{"start_ms":"397768","end_ms":"399598","text":"and then once there's a primer,","start_time_text":"6:37"},{"start_ms":"399598","end_ms":"404238","text":"then DNA polymerase can just\nstart adding nucleotides,","start_time_text":"6:39"},{"start_ms":"404239","end_ms":"407159","text":"it can start adding\nnucleotides at the 3' end.","start_time_text":"6:44"},{"start_ms":"407159","end_ms":"409430","text":"And the reason why the leading\nstrand has it pretty easy","start_time_text":"6:47"},{"start_ms":"409430","end_ms":"412680","text":"is this DNA polymerase right over here,","start_time_text":"6:49"},{"start_ms":"413613","end_ms":"415692","text":"this polymerase, and once again,","start_time_text":"6:53"},{"start_ms":"415692","end_ms":"419107","text":"they aren't these perfect\nrectangles as on this diagram.","start_time_text":"6:55"},{"start_ms":"419107","end_ms":"421326","text":"They're actually much more\nfascinating than that.","start_time_text":"6:59"},{"start_ms":"421326","end_ms":"422711","text":"You see the polymerase up there,","start_time_text":"7:01"},{"start_ms":"422712","end_ms":"427079","text":"you also see you one\nover here, polymerase.","start_time_text":"7:02"},{"start_ms":"427079","end_ms":"428477","text":"This polymerase can just,","start_time_text":"7:07"},{"start_ms":"428477","end_ms":"431600","text":"you can kind of think of it\nas following the opened zipper","start_time_text":"7:08"},{"start_ms":"431601","end_ms":"433473","text":"and then just keep adding,","start_time_text":"7:11"},{"start_ms":"433473","end_ms":"437190","text":"keep adding nucleotides at the 3' end.","start_time_text":"7:13"},{"start_ms":"437191","end_ms":"440831","text":"And so this one seems\npretty straightforward.","start_time_text":"7:17"},{"start_ms":"440831","end_ms":"443232","text":"Now, you might say wouldn't it be easy","start_time_text":"7:20"},{"start_ms":"443232","end_ms":"446893","text":"if we could just add\nnucleotides at a 5' end,","start_time_text":"7:23"},{"start_ms":"446893","end_ms":"448433","text":"because then we could say","start_time_text":"7:26"},{"start_ms":"448433","end_ms":"451128","text":"well this is going from 3' to 5',","start_time_text":"7:28"},{"start_ms":"451128","end_ms":"453399","text":"well maybe that polymerase\nor different polymerase","start_time_text":"7:31"},{"start_ms":"453399","end_ms":"455563","text":"could just keep adding\nnucleotides like that,","start_time_text":"7:33"},{"start_ms":"455563","end_ms":"457307","text":"and then everything would be easy.","start_time_text":"7:35"},{"start_ms":"457308","end_ms":"460011","text":"Well, it turns out that\nthat is not the case.","start_time_text":"7:37"},{"start_ms":"460011","end_ms":"463840","text":"you cannot add nucleotides at the 5' end,","start