Jesus, finally someone explained this properly. this is the 10th clip I watched and now can understand this end replication problem. thank you for sharing.
just reading about histone codes and the histone sequence in human. is very complex for me. that is about heterochromatin, euchromatin and histone tails, x chromosome deactivation, methylation and acetylation of histones affecting epigenetic and genetics. I wish you was here to read this with me.
Woow .. interesting topics ... I will try to speak about them in my coming videos maybe next week .. so stay arround ;) .. this week I am working on PCR and rt-PCR the video will be up tomorrow I think ...
There's quite a few things missing in this video. Especially, since we're talking about the end replication problem, there is a need to mention that the lagging strand and its template strand never really fully get replicated, there's always a part of the extended DNA that doesn't get replicated. The telomere essentially has both double stranded and single stranded regions, the single stranded region of the telomere loops around and forms a knot in the telomeric region which stabilizes the ends of DNA.
If replication of large eukaryotic chromosome is initiated at multiple origins of replication ( replication bubbles) the end replication problem should probably happen on each replication bubble. Why it only happens at telomere?
@@hyderali692 I think it's because each replication fork eventually runs into a replication fork running in the opposite direction (they meet). So all of the DNA is replicated there.
@@haykojan6590 if you don't care about learning material as close as accurate, as possible, I am sorry. If I had the academia and time to create a video, I would. However, I am no one to do so, just like you. Just stating an opinion based on what I have learned from professionals. If you don't like my comment and are offended, then maybe science is not for you. There is a lot of criticism and people, just like myself make and learn from mistakes! That is the beautiful thing about science. God bless you and best of luck in your path to success.
Like other students, I finally found it explained correctly and logically after a lot of unuseful videos. The most convincing explanation of telomeres. Thanks alot.
Thank you for the nice explanation. I am wondering why only lagging strands are facing telomere shortenings, why not the leading strands as they also had primer at their starting points and there is no way to replace it with DNA? Could you please explain?
Thank u so much. This is the best video on UA-cam explaining the end replication problem and its solution by telomerase enzyme. Really very helpful video for students. God bless u !!
I have watched many videos before, but yours is exceptional and well-detailed. You helped me understand in 13 minutes what I had been struggling with for 1 hour ❤️❤️❤️👍🏻👍🏻👍🏻. Thanks a lot.
thank you for this explanation, I've been trying to get my head around this for hours but every other explanation on the internet is awful, so thank you for saving me!
OK, so you forgot to mention that there is a rna primer at the beginning of the leading strand, so how is that rna primer replaced cuz if the exonuclease removes it there isn't a 3' for the dna polymerase to attach to?
this is exactly the same question that has been haunting me for hours! I've watched a lot of videos about the end replication problem but they all forgot to mention that there is a primer at the begginng of the leading strand too! Someone please help me I can't find the explanation for this anywhere :(
because leading strand's primer is somewhere within the DNA, it will eventually be filled by dna coming from the leading strand of the previous replication fork.
That is done in prokaryotes by DNA Polymerase I. It has a unique 5' to 3' exonuclease activity that can replace the RNA primer and then replace it with DNA. In Eukaryotes the removal is done by RNase H and Flap Endonucleases
at 10:03, when the parent strand is elongated by the Telomerase and the rna primer comes and the daughter strand is completed, what happens to the part where the rna primer and parent strand disappears in the video?
This is the best explanation I have ever seen on this topic.Finally I have clear my doubts regarding this topic.Thank you so much for clearing my doubts . I wish you will keep it up always.
Hi! Thank you so much for uploading this! I am just very confused about one thing - why would this not happened on BOTH the lagging AND leading strand? In both cases there is no OH for the new nucleotide to be added to when filling in primers at the end. Afterall wasnt the leading strand also started with a primer as well? Why can that one get filled in easily but the one at the end of the lagging strand cause such a problem? Thank you so much for you help in advance!
In the leading strand there is only one RNA primer at the beginning of the daughter strand. At the end of DNA replication this RNA primer is removed nucleotide by nucleotide and each removed nucleotide is replaced by a DNA nucleotide using an enzyme called DNA polymerase (I), this sequence of DNA which replaces the removed RNA primer is then linked with the rest of the daughter strand using the enzyme Ligase. Now you may ask why this does not happen in the lagging strand? the problem is that the mechanism of replication is totally different in the lagging strand, because there are many RNA primers, each one of them has a different sequence, these RNA primers are removed all at once, then the gaps are filled normally with DNA polymerase starting from each OKAZAKI fragment, but this enzyme usually forgets to replace the last RNA primer because of the missing of -OH, so this enzyme does not sense the absence of the last strand which is rather sensed by the enzyme telomerase which in turn fixes this issue. I hope I answered your question.
Great video, but I have a question. Around 10:12 after the daughter (red) DNA strand is completed from the -OH of the new RNA primer (Green), but it seems like the end replication problem will still there after the RNA primer is removed, but at 10:13 the RNA primer is removed ALONG with the extra piece of the parent DNA strand (blue). Why is that end of the DNA cut now but didn't happen in the original end replication problem? It seems cutting the extra end of the DNA would solve the issue from the beginning? By the way, is this Maria Konovalenko? I was just watching some of her videos about telomeres and aging and then came across this video, and the accent sounds slightly similar. Could be coincidence, lol. Anyway, thanks for the video!
Hey, actually not because if you watch around 9:41 you see that the original DNA strand has been elongated, so what is cut in 10:13 is the extra peace of DNA strand and not a part of the original one, in this case we save the original strand which is the target. And no actually this is not Maria Konovalenko, my name is Rita. Thank you for your comment, and stay around many interesting videos are coming up, if you have suggestions about other topics you can tell me :)
Thanku so very much ma'am ...I have so much confusion regarding this topic...Bt by the help of your video my every confusion gets clear.again TSM...ma'am
Ok so I want to clarify something. The last primer on the lagging strand is removed because it is RNA and under physiological conditions is extremely unstable. RNase will remove it THAT"s WHY IT IS REMOVED.
Hi, I'm not sure if anybody has pointed this out or it may be just be but @5:12 , isn't the 5'-3' meant to be the leading strand whilst the 3'-5' is the lagging strand?
One question - so telomerase extends the parent strand, RNA primer is synthesised, gap filled in by DNA polymerase. At minute 10:12, won't the RNA primer be removed, leaving a 3' overhang with no hydroxyl so the end replication problem is repeated over and over again? And if telomerase keeps extending the parent strand in the same way, does aging relate to the rate of cell division being much higher than the rate at which telomeres are expanded - i.e. telomeres do end up shorter as we age?
Hello, the telomerase extends the telomere in order to provide extra bases on which the RNA primer can hybridize, so we are not interested in copying this extra strand because it is not a part of the original strand, if you notice at 10.14 even after the RNA primer is removed the original strand is still completely copied, and so the original strand is conserved and this is the important thing. And yes, as I said from 10.30 Telomerase does not exist always in sufficient amount so shortening does happen contentiously during an individual life, and the level of Telomerase decreases during the life which then increases the incidence of DNA shortening as the individual ages up, at a certain age the levels of Telomerase inside the cells become so reduced. On the other hand, cancer cells were found to have higher amount of Telomerase which is one of the reasons that make the cancer cell immortal, because it does not age up. I hope that I answered your question.
Hello, No actually .. the end replication problem happens only with the lagging strand .. as I said the copying of the leading strands happens normally from 5` to 3` with no problems ..
Biomedical and Biological Sciences but Im confused about this, as after the primer removel in both strands leading as well as lagging strand results in the formation of DNA shorter in daughter strands in both cases. as this happens to both because there is primer in both the newly strands at 5' end .... so how could it be the only with lagging strand ... and if so then how leading strand is overcoming this problem of 5' end shortening.. please Explain.
In the leading strand there is only one RNA primer at the beginning of the daughter strand. At the end of DNA replication this RNA primer is removed nucleotide by nucleotide and each removed nucleotide is replaced by a DNA nucleotide using an enzyme called DNA polymerase (I), this sequence of DNA which replaces the removed RNA primer is then linked with the rest of the daughter strand using the enzyme Ligase. Now you may ask why this does not happen in the lagging strand? the problem is that the mechanism of replication is totally different in the lagging strand, because there are many RNA primers, each one of them has a different sequence, these RNA primers are removed all at once, then the gaps are filled normally with DNA polymerase starting from each OKAZAKI fragment, but this enzyme usually forgets to replace the last RNA primer because of the missing of -OH, so this enzyme does not sense the absence of the last strand which is rather sensed by the enzyme telomerase which in turn fixes this issue. I hope I answered your question.
I would like to ask a question. If as you said RNA primer at the end can not replaced because of lack of free OH group, then how RNA primer in the leading strand is replaced? Because the begining part is 5' which is continuously written by DNA polymerase and lack OH group.
you actually didn't mention the fact that the telomere has a single stranded region in the 3 prime end and you also didn't mention how the dna polymerase replicates, the part where you explain the replication of the telomere is completely incorrect
How can the first daughter dna thread be built from 5 to 3 in the 3 to 5 sequence when there is no OH mould for the first nucleotide to be built on ? Or the forst nucleotide doesn't need an OH ?
Jesus, finally someone explained this properly. this is the 10th clip I watched and now can understand this end replication problem. thank you for sharing.
Oh thank you for your comment, I will try to keep making such videos. And if you have suggestions for other topics, it would be nice to hear them :)
just reading about histone codes and the histone sequence in human. is very complex for me. that is about heterochromatin, euchromatin and histone tails, x chromosome deactivation, methylation and acetylation of histones affecting epigenetic and genetics. I wish you was here to read this with me.
Woow .. interesting topics ... I will try to speak about them in my coming videos maybe next week .. so stay arround ;) .. this week I am working on PCR and rt-PCR the video will be up tomorrow I think ...
Hey .. I thing that you might appreciate this video .. Check it out ;)
ua-cam.com/video/bNjjAoyWs6I/v-deo.html
I second this. This explanation really tied everything together nicely for me.
There's quite a few things missing in this video. Especially, since we're talking about the end replication problem, there is a need to mention that the lagging strand and its template strand never really fully get replicated, there's always a part of the extended DNA that doesn't get replicated. The telomere essentially has both double stranded and single stranded regions, the single stranded region of the telomere loops around and forms a knot in the telomeric region which stabilizes the ends of DNA.
inaccurate video. sorry
If replication of large eukaryotic chromosome is initiated at multiple origins of replication ( replication bubbles) the end replication problem should probably happen on each replication bubble. Why it only happens at telomere?
@@hyderali692 I think it's because each replication fork eventually runs into a replication fork running in the opposite direction (they meet). So all of the DNA is replicated there.
@@jorgeeduardocarrenozapata4243 if you can explain it better, then create a video that explains it buddy.... otherwise take your comments elsewhere
@@haykojan6590 if you don't care about learning material as close as accurate, as possible, I am sorry. If I had the academia and time to create a video, I would. However, I am no one to do so, just like you. Just stating an opinion based on what I have learned from professionals. If you don't like my comment and are offended, then maybe science is not for you. There is a lot of criticism and people, just like myself make and learn from mistakes! That is the beautiful thing about science. God bless you and best of luck in your path to success.
Like other students, I finally found it explained correctly and logically after a lot of unuseful videos. The most convincing explanation of telomeres. Thanks alot.
Only video in the whole UA-cam to explain the concept properly
The best explanation so far... I would not have understood it without this video... God bless the teacher
This topic of genetics is so interesting. I hope I'll have the chance to study and research it once I've graduated. :D
Same!
Best explaination of telomeres and telomerase
Thank you for your comment ... stay around many interesting videos are coming up :)
I must have watched and read dozens of videos and articles on this topic...I finally get it now! thank you for this video.
Thank you for the nice explanation. I am wondering why only lagging strands are facing telomere shortenings, why not the leading strands as they also had primer at their starting points and there is no way to replace it with DNA? Could you please explain?
Thank u so much. This is the best video on UA-cam explaining the end replication problem and its solution by telomerase enzyme. Really very helpful video for students. God bless u !!
Your way of explaining complicated topics in such an easy way is awesome.
Finally someone can explain it good job👏
Thank you for the comment ... stay tuned :)
i swear to God, am blown away... this is so amazing!!!
Oh my god thank you so much, I watched literally every video about this topic and then finally found a good and detailed explanation!! Finally 🤯
I have watched many videos before, but yours is exceptional and well-detailed. You helped me understand in 13 minutes what I had been struggling with for 1 hour ❤️❤️❤️👍🏻👍🏻👍🏻. Thanks a lot.
Thank you! Finally!! By far the best video I’ve seen.
U deserve the world
thank you for this explanation, I've been trying to get my head around this for hours but every other explanation on the internet is awful, so thank you for saving me!
The best explanation I have ever found related to this topic,, I mean she made it more interesting.
Thank you for explaining why replication can go only one direction. :)
A very big thanks to u .....after half an hour waste....found u and now it's clear
The best explanation i heve found on this specific topic. Great. Very simple explanation, it's like you are watching what my mind needs❤
My teacher uses imagens from your video to teach about telomers in molecular biology, great job.
best video ive seen so far explaining this topic!!
you are a real master!! I could understand EVERYTHING at once!! I love it!!
Finally someone explained it correctly, nice and easy
One of the best video for Telomerase explaination
This is the best explanation i found. Thank you very much.
VERY CLEVER; WELL DONE, THE PROBLEM IS WHEN THE PRIMERS ARE REMOVED THE END LAGGING STRAND IS NOT "COVERED DOWN"...now i got it; good job ma'am:)
Clearly narrated a beautiful story. Well explained. A layman like me can understand well. Thank you.
OK, so you forgot to mention that there is a rna primer at the beginning of the leading strand, so how is that rna primer replaced cuz if the exonuclease removes it there isn't a 3' for the dna polymerase to attach to?
Ligase?
this is exactly the same question that has been haunting me for hours! I've watched a lot of videos about the end replication problem but they all forgot to mention that there is a primer at the begginng of the leading strand too! Someone please help me I can't find the explanation for this anywhere :(
because leading strand's primer is somewhere within the DNA, it will eventually be filled by dna coming from the leading strand of the previous replication fork.
That is done in prokaryotes by DNA Polymerase I. It has a unique 5' to 3' exonuclease activity that can replace the RNA primer and then replace it with DNA. In Eukaryotes the removal is done by RNase H and Flap Endonucleases
Ultimately the short gaps are joined by DNA Ligase
this has always been a problem and finally,
you've explained to the best of my understanding
thank you very much for the extremely good work.
Much appreciated!! I was puzzled with it when reviewing cell biology and now I get it!
Great video! I've been looking for someone to draw out how telomerase works and you did a great job with it! Thank you so much
this is the best explanation i have found. thank you!
I really don't know how to thank you, you helped a lot.
Great video, you explained it really well! I finally got it
Thank you ... stay tuned :)
This is such a perfect and straight-forward explanation - thank you
at 10:03, when the parent strand is elongated by the Telomerase and the rna primer comes and the daughter strand is completed, what happens to the part where the rna primer and parent strand disappears in the video?
I suppose they are degraded by endonucleases
This is the best explanation I have ever seen on this topic.Finally I have clear my doubts regarding this topic.Thank you so much for clearing my doubts . I wish you will keep it up always.
Thank you! Very easy to understand, brief and to the point.
Nice Explained. Respect from India🇮🇳🇮🇳🇮🇳
I don't understand where does the primer come from @9:56 and how does the completion happen afterwards?
Hi! Thank you so much for uploading this! I am just very confused about one thing - why would this not happened on BOTH the lagging AND leading strand? In both cases there is no OH for the new nucleotide to be added to when filling in primers at the end. Afterall wasnt the leading strand also started with a primer as well? Why can that one get filled in easily but the one at the end of the lagging strand cause such a problem? Thank you so much for you help in advance!
In the leading strand there is only one RNA primer at the beginning of the daughter strand. At the end of DNA replication this RNA primer is removed nucleotide by nucleotide and each removed nucleotide is replaced by a DNA nucleotide using an enzyme called DNA polymerase (I), this sequence of DNA which replaces the removed RNA primer is then linked with the rest of the daughter strand using the enzyme Ligase. Now you may ask why this does not happen in the lagging strand? the problem is that the mechanism of replication is totally different in the lagging strand, because there are many RNA primers, each one of them has a different sequence, these RNA primers are removed all at once, then the gaps are filled normally with DNA polymerase starting from each OKAZAKI fragment, but this enzyme usually forgets to replace the last RNA primer because of the missing of -OH, so this enzyme does not sense the absence of the last strand which is rather sensed by the enzyme telomerase which in turn fixes this issue. I hope I answered your question.
It was a great video which gave me full comprehension of telomerase and DNA shortening. Thank You very much
Thanks god I patiently watch till the end and finally get sth from u
Your videos are phenomenal! Thank you & keep it up!
WOW, thank you .. such a comment encourages me to keep up :)
Finally after looking for so many videos...understood well....thanks a lot👌👌👍👍👍
Best explanation indeed
Thanks for sharing
Thank you so much for clarifying the telomere issue.
wow...your explanation is great. Just what i needed. Thank you.
this really simplified it for me, thank u so much
What a clear and wonderful explanation...
thank you so much...i struggled to understand this in class but now i totally get whats going on
Thanks for your intellects explanation about the Telomerase and the end replication problem.
Best video for the DNA replication! Thank you
Best explanation on YT
This was the best explanation I ever heard 👌that was extremely awesome. Thank you
Good explanation i have ever seen about telomarase
Thank you so much for this video, seriously I was so lost but this saved me before my exam😭❤️
Oh my god thank you!! I finally found a detailed explanation 🤯
Keep up the good work, this was really helpful
this is very beautifully explained
good job...you explain the actual reason behind this telomer problem
thanks a lot for explaining complex idea in simple manner. your diagrams are easy to visualize. beautiful
Thank you :D
THANK YOU FOR THIS!
Thanks so much
really helpful after watching 4 vids
Great video, but I have a question. Around 10:12 after the daughter (red) DNA strand is completed from the -OH of the new RNA primer (Green), but it seems like the end replication problem will still there after the RNA primer is removed, but at 10:13 the RNA primer is removed ALONG with the extra piece of the parent DNA strand (blue). Why is that end of the DNA cut now but didn't happen in the original end replication problem? It seems cutting the extra end of the DNA would solve the issue from the beginning?
By the way, is this Maria Konovalenko? I was just watching some of her videos about telomeres and aging and then came across this video, and the accent sounds slightly similar. Could be coincidence, lol. Anyway, thanks for the video!
Hey, actually not because if you watch around 9:41 you see that the original DNA strand has been elongated, so what is cut in 10:13 is the extra peace of DNA strand and not a part of the original one, in this case we save the original strand which is the target.
And no actually this is not Maria Konovalenko, my name is Rita.
Thank you for your comment, and stay around many interesting videos are coming up, if you have suggestions about other topics you can tell me :)
Thanku so very much ma'am ...I have so much confusion regarding this topic...Bt by the help of your video my every confusion gets clear.again TSM...ma'am
Amazing explanation, thank you ... I subscribed to this channel hoping to encourage you do more amazing videos like this.
Ok so good video. Now how do we extend them. How or what can be used to stop the shortening ?
Very nice and neat explanation
Also Thankyou so much, this is a great description!
Ok so I want to clarify something. The last primer on the lagging strand is removed because it is RNA and under physiological conditions is extremely unstable. RNase will remove it THAT"s WHY IT IS REMOVED.
Hi, I'm not sure if anybody has pointed this out or it may be just be but @5:12 , isn't the 5'-3' meant to be the leading strand whilst the 3'-5' is the lagging strand?
Leading strand doesn’t require primer to start elongation????
Many thanks! It is very helpful!!
Thank you so much for keeping it simple 🙌
Very helpful .Thank YOU!
I would recommend this video. it makes bio 221 concepts easy
Thank you for your comment ..
*Why did you stop making videos?!* :( :( :( :( :(
Great! simple and to the point
One question - so telomerase extends the parent strand, RNA primer is synthesised, gap filled in by DNA polymerase. At minute 10:12, won't the RNA primer be removed, leaving a 3' overhang with no hydroxyl so the end replication problem is repeated over and over again? And if telomerase keeps extending the parent strand in the same way, does aging relate to the rate of cell division being much higher than the rate at which telomeres are expanded - i.e. telomeres do end up shorter as we age?
Hello, the telomerase extends the telomere in order to provide extra bases on which the RNA primer can hybridize, so we are not interested in copying this extra strand because it is not a part of the original strand, if you notice at 10.14 even after the RNA primer is removed the original strand is still completely copied, and so the original strand is conserved and this is the important thing. And yes, as I said from 10.30 Telomerase does not exist always in sufficient amount so shortening does happen contentiously during an individual life, and the level of Telomerase decreases during the life which then increases the incidence of DNA shortening as the individual ages up, at a certain age the levels of Telomerase inside the cells become so reduced. On the other hand, cancer cells were found to have higher amount of Telomerase which is one of the reasons that make the cancer cell immortal, because it does not age up. I hope that I answered your question.
I Love you 😍😍
Best teacher ever
Amazing explanation ma'am ... Thank you so much .... Understood very clearly 😊😊
Wonderful explanation. Thank you
very good explanation Love it
It helped a lot..it was really good..alwYs stay blessed..
Thanks very much I hope you continue
Wow👏👏🙌🙌👏👏🙌🙌👏👏🙌🙌 Thank you Soooo sooo much, I didn't understand this the whole semester... But thanks to you I finally do 🙌❤️
Thank you 🙏. You are the best
thank you from Saudi Arabia
1:00 Shouldn't it say 92 telemeres in each female cell, and 91 in males? I assume the Y chromosome has 3, not 4.
isnt this problem happening with leading strand as u talk about only lagging strand
Hello, No actually .. the end replication problem happens only with the lagging strand .. as I said the copying of the leading strands happens normally from 5` to 3` with no problems ..
Biomedical and Biological Sciences
but Im confused about this, as after the primer removel in both strands leading as well as lagging strand results in the formation of DNA shorter in daughter strands in both cases. as this happens to both because there is primer in both the newly strands at 5' end .... so how could it be the only with lagging strand ... and if so then how leading strand is overcoming this problem of 5' end shortening.. please Explain.
In the leading strand there is only one RNA primer at the beginning of the daughter strand. At the end of DNA replication this RNA primer is removed nucleotide by nucleotide and each removed nucleotide is replaced by a DNA nucleotide using an enzyme called DNA polymerase (I), this sequence of DNA which replaces the removed RNA primer is then linked with the rest of the daughter strand using the enzyme Ligase. Now you may ask why this does not happen in the lagging strand? the problem is that the mechanism of replication is totally different in the lagging strand, because there are many RNA primers, each one of them has a different sequence, these RNA primers are removed all at once, then the gaps are filled normally with DNA polymerase starting from each OKAZAKI fragment, but this enzyme usually forgets to replace the last RNA primer because of the missing of -OH, so this enzyme does not sense the absence of the last strand which is rather sensed by the enzyme telomerase which in turn fixes this issue. I hope I answered your question.
Perfect explination 💙 thank you 💙
Thank you so much this really really helped!!!
I would like to ask a question. If as you said RNA primer at the end can not replaced because of lack of free OH group, then how RNA primer in the leading strand is replaced? Because the begining part is 5' which is continuously written by DNA polymerase and lack OH group.
you actually didn't mention the fact that the telomere has a single stranded region in the 3 prime end and you also didn't mention how the dna polymerase replicates, the part where you explain the replication of the telomere is completely incorrect
How can the first daughter dna thread be built from 5 to 3 in the 3 to 5 sequence when there is no OH mould for the first nucleotide to be built on ? Or the forst nucleotide doesn't need an OH ?