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 RUclips explaining the end replication problem and its solution by telomerase enzyme. Really very helpful video for students. God bless u !!
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
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.
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.
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.
in my book it says that at the end of the lagging strand you can't even attach a RNA primer because helicase goes away and without it, RNA-primase cannot attach a primer.
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
This video is only partially correct. Usually the primer removal of the 5‘ end of the lagging strand doesn’t not affect the telomere length as much, as it is recessed anyways to generate the 3‘ overhang. The problem persists in the leading strand, which has lost its overhang. Therefore the 5‘ end of the parental strand needs to be recessed leading to DNA loss as in the next round of replication the 5‘ end gets shorter and shorter. It’s not so much about the primer removal, which causes the end replication problem. Find the full explanation at Hug and Lingner, Chromosoma, 2006.
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
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?
Thank you for excellent and informative presentation."The telomere is involved in several essential biological functions. It protects chromosomes from recombination, end-to end fusion, and recognition as damaged DNA; provides a means for complete replication of chromosomes; contributes to the functional organization of chromosomes within the nucleus; participates in the regulation of gene expression; and serves as a molecular clock that controls the replicative capacity of human cells and their entry into senescence."
Part of evolutionary senescent theory suggests that telomere shortening and senescent cell cycle arrest acts as a protective mechanism against cancer. There is a trade off between long telomeres allowing frequent continual cell replication, but cumulative DNA damage leading to cancer later in life Vs. short telomeres triggering tumour suppressor genes, e.g., p53, arrested cell cycle, cell senescence states or apoptosis, reducing the likelihood of cancer. In other words telomere shortening may be a necessity for organisms that live longer in less egregious environments and are able to reproduce in old age. Therefore, simply elongating telomeres as a way of extending life may not be a viable option.
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?
Still don’t get why it can’t go from 3 to 5 based on this explanation. After all, each nucleotide has both a P and a OH available to be added onto from either pole. My guess is it is to do with the binding sequence and conformational changes necessary for DNA polymerase to function properly in the interaction with nucleotides.
Thanks for this awesome video❤🌸 But, I think this problem occure in the leading strand also Because the start site at 5' end contain a primer which must be removed after replication So ther is a gap will be formed.
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.
As long as the telomeres are there at ends, no gene will be lost so no loss of function. Hence, if we still have 5000bp telomere left at late age then how can we say that shortening of telomere leads to aging?
There is one thing that I don't understand- we also have a primer on the 5' end of the leading strand and when we take it off we are left without an OH group (right?). How can it be that the end replication problem doesn't happen in the leading strand as well?
Anyway to reverse loss of telomeres? Once we learn how to clear harmful senescent cells we'll need to replace them with healthy cells which increases our bodies age. Maybe increasing our health, but ultimately reducing life I assume.
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 ?
There is one question If RNA primer in lagging strande 5'end is removed which creates problem lack of 3'OH group. Then RNA primer in leading strande 5'end is also removed. But there is no end problem.
Rna primer is needed in the leading strand too at the beginning of replication..then why dont leading strand end face the same problem as there wont be a hydroxyl group available there too??
You have switched lagging and leading strands. The leading strand is the side that has telomerase! Lagging strands can be replicated right until the end; it is the side that is replicated discontinuously away from the fork.
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? Please help me bro.
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 ;)
ruclips.net/video/bNjjAoyWs6I/видео.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 RUclips to explain the concept properly
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?
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!
The best explanation so far... I would not have understood it without this video... God bless the teacher
Best explaination of telomeres and telomerase
Thank you for your comment ... stay around many interesting videos are coming up :)
Finally someone can explain it good job👏
Thank you for the comment ... stay tuned :)
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 🤯
Your way of explaining complicated topics in such an easy way is awesome.
I must have watched and read dozens of videos and articles on this topic...I finally get it now! thank you for this video.
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:)
Thank u so much. This is the best video on RUclips explaining the end replication problem and its solution by telomerase enzyme. Really very helpful video for students. God bless u !!
The best explanation I have ever found related to this topic,, I mean she made it more interesting.
A very big thanks to u .....after half an hour waste....found u and now it's clear
Thank you so much for this video, seriously I was so lost but this saved me before my exam😭❤️
Clearly narrated a beautiful story. Well explained. A layman like me can understand well. Thank you.
Thank you for explaining why replication can go only one direction. :)
My teacher uses imagens from your video to teach about telomers in molecular biology, great job.
Nice Explained. Respect from India🇮🇳🇮🇳🇮🇳
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?
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.
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.
i swear to God, am blown away... this is so amazing!!!
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.
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.
This is the best explanation i found. Thank you very much.
Finally someone explained it correctly, nice and easy
thanks a lot for explaining complex idea in simple manner. your diagrams are easy to visualize. beautiful
Thank you :D
you are a real master!! I could understand EVERYTHING at once!! I love 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
in my book it says that at the end of the lagging strand you can't even attach a RNA primer because helicase goes away and without it, RNA-primase cannot attach a primer.
It was a great video which gave me full comprehension of telomerase and DNA shortening. Thank You very much
U deserve the world
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
Finally someone could help me understand this!!!
Finally after looking for so many videos...understood well....thanks a lot👌👌👍👍👍
Best explanation indeed
Thanks for sharing
this really simplified it for me, thank u so much
This is such a perfect and straight-forward explanation - thank you
This video is only partially correct. Usually the primer removal of the 5‘ end of the lagging strand doesn’t not affect the telomere length as much, as it is recessed anyways to generate the 3‘ overhang. The problem persists in the leading strand, which has lost its overhang. Therefore the 5‘ end of the parental strand needs to be recessed leading to DNA loss as in the next round of replication the 5‘ end gets shorter and shorter. It’s not so much about the primer removal, which causes the end replication problem. Find the full explanation at Hug and Lingner, Chromosoma, 2006.
One of the best video for Telomerase explaination
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
Great video, you explained it really well! I finally got it
Thank you ... stay tuned :)
Wow👏👏🙌🙌👏👏🙌🙌👏👏🙌🙌 Thank you Soooo sooo much, I didn't understand this the whole semester... But thanks to you I finally do 🙌❤️
good job...you explain the actual reason behind this telomer problem
Thank you! Finally!! By far the best video I’ve seen.
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 process continues...I guess
Thank you for excellent and informative presentation."The telomere is involved in several essential biological functions. It protects chromosomes from recombination, end-to end fusion, and recognition as damaged DNA; provides a means for complete replication of chromosomes; contributes to the functional organization of chromosomes within the nucleus; participates in the regulation of gene expression; and serves as a molecular clock that controls the replicative capacity of human cells and their entry into senescence."
You are right ... it has a great impact in the cell ..
Much appreciated!! I was puzzled with it when reviewing cell biology and now I get it!
Part of evolutionary senescent theory suggests that telomere shortening and senescent cell cycle arrest acts as a protective mechanism against cancer. There is a trade off between long telomeres allowing frequent continual cell replication, but cumulative DNA damage leading to cancer later in life Vs. short telomeres triggering tumour suppressor genes, e.g., p53, arrested cell cycle, cell senescence states or apoptosis, reducing the likelihood of cancer. In other words telomere shortening may be a necessity for organisms that live longer in less egregious environments and are able to reproduce in old age. Therefore, simply elongating telomeres as a way of extending life may not be a viable option.
this is the best explanation i have found. thank you!
Thank you! Very easy to understand, brief and to the point.
Thanks for your intellects explanation about the Telomerase and the end replication problem.
This was the best explanation I ever heard 👌that was extremely awesome. Thank you
best video ive seen so far explaining this topic!!
Amazing explanation ma'am ... Thank you so much .... Understood very clearly 😊😊
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?
Still don’t get why it can’t go from 3 to 5 based on this explanation. After all, each nucleotide has both a P and a OH available to be added onto from either pole. My guess is it is to do with the binding sequence and conformational changes necessary for DNA polymerase to function properly in the interaction with nucleotides.
thank you so much...i struggled to understand this in class but now i totally get whats going on
I really don't know how to thank you, you helped a lot.
Thanks for this awesome video❤🌸
But, I think this problem occure in the leading strand also
Because the start site at 5' end contain a primer which must be removed after replication So ther is a gap will be formed.
really helpful after watching 4 vids
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.
As long as the telomeres are there at ends, no gene will be lost so no loss of function. Hence, if we still have 5000bp telomere left at late age then how can we say that shortening of telomere leads to aging?
Thanks god I patiently watch till the end and finally get sth from u
wow...your explanation is great. Just what i needed. Thank you.
Thank you so much for clarifying the telomere issue.
I would recommend this video. it makes bio 221 concepts easy
Thank you for your comment ..
thank you so much now i wont fail my test tomorrow
Your videos are phenomenal! Thank you & keep it up!
WOW, thank you .. such a comment encourages me to keep up :)
THANK YOU FOR THIS!
There is one thing that I don't understand- we also have a primer on the 5' end of the leading strand and when we take it off we are left without an OH group (right?). How can it be that the end replication problem doesn't happen in the leading strand as well?
It will connect with the one close to it i.e the second one so the bond is formed
Very interesting. So in the end replication, the parent DNA extension is cut off and disappears like the RNAs.
Anyway to reverse loss of telomeres? Once we learn how to clear harmful senescent cells we'll need to replace them with healthy cells which increases our bodies age. Maybe increasing our health, but ultimately reducing life I assume.
Best explanation on YT
Oh my god thank you!! I finally found a detailed explanation 🤯
Ok so good video. Now how do we extend them. How or what can be used to stop the shortening ?
Leading strand doesn’t require primer to start elongation????
What a clear and wonderful explanation...
so i have problem like that, if telomere is superhelix structure it curls or gets destroyed as one strand is proper length and other is not?
I don't understand where does the primer come from @9:56 and how does the completion happen afterwards?
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 ?
Very nice and neat explanation
What about fused Telomeres...Genetic Tampering ?
this is very beautifully explained
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.
There is one question
If RNA primer in lagging strande 5'end is removed which creates problem lack of 3'OH group. Then RNA primer in leading strande 5'end is also removed. But there is no end problem.
Rna primer is needed in the leading strand too at the beginning of replication..then why dont leading strand end face the same problem as there wont be a hydroxyl group available there too??
excellent question...i understand every aspect of this topic, but what is about the leading strand.
Tthank you so much you help me with my studies for the exams
Thanks very much I hope you continue
I want to tell you that the problem is on both strands. how the primer of the leading strand is replaced without any problems ??
Best video for the DNA replication! Thank you
Good explanation i have ever seen about telomarase
Amazing explanation, thank you ... I subscribed to this channel hoping to encourage you do more amazing videos like this.
Keep up the good work, this was really helpful
Thank you so much for keeping it simple 🙌
You have switched lagging and leading strands. The leading strand is the side that has telomerase! Lagging strands can be replicated right until the end; it is the side that is replicated discontinuously away from the fork.
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?
Please help me bro.