A full explanation about the Telomerase and the end replication problem

[@djalitanaful]

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.

[@biomedicalandbiologicalsci4989]

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 :)

[@djalitanaful]

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.

[@biomedicalandbiologicalsci4989]

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 ...

[@biomedicalandbiologicalsci4989]

Hey .. I thing that you might appreciate this video .. Check it out ;) kzbin.info/www/bejne/mH_Nm3SlrrymbKs

[@ns9176]

I second this. This explanation really tied everything together nicely for me.

[@aparnakanjhlia5141]

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.

[@jorgeeduardocarrenozapata4243]

inaccurate video. sorry

[@hyderali692]

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?

[@veronikabacova9467]

@@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]

@@jorgeeduardocarrenozapata4243 if you can explain it better, then create a video that explains it buddy.... otherwise take your comments elsewhere

[@jorgeeduardocarrenozapata4243]

@@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.

[@mamunrashid4816]

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?

[@sahanapaulganesan6309]

Only video in the whole KZbin to explain the concept properly

[@dr.m.umairmajeed1213]

Best explaination of telomeres and telomerase

[@biomedicalandbiologicalsci4989]

Thank you for your comment ... stay around many interesting videos are coming up :)

[@katharinamazzotti6349]

This topic of genetics is so interesting. I hope I'll have the chance to study and research it once I've graduated. :D

[@kameliasali9639]

Same!

[@andjelanovakovic5006]

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?

[@XDSome1XD]

Ligase?

[@AL-yj1vk]

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 :(

[@hughdong4593]

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.

[@avikchaudhuri8515]

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

[@avikchaudhuri8515]

Ultimately the short gaps are joined by DNA Ligase

[@superEriccui]

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.

[@ali_karem055]

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.

[@vasokalamara1827]

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

[@akro80]

Finally someone can explain it good job👏

[@biomedicalandbiologicalsci4989]

Thank you for the comment ... stay tuned :)

[@graw96]

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!

[@biomedicalandbiologicalsci4989]

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.

[@azca.]

Tip: Play this 1.25x speed

[@IntangibleGracie]

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?

[@ciprianmatei1731]

I suppose they are degraded by endonucleases

[@tanimasaha56]

This process continues...I guess

[@Nongthoi9344]

I have a question :- for synthesis of leading strand RNA primer is required at the very beginning, which will be later on removed. How will this gap be filled? Since extension occurs from 5 to 3. But in this case exposed 5 ends.

[@Stephenbashqier]

Great video, you explained it really well! I finally got it

[@biomedicalandbiologicalsci4989]

Thank you ... stay tuned :)

[@tataritka]

Thank you for explaining why replication can go only one direction. :)

[@Biomeducated]

*Why did you stop making videos?!* :( :( :( :( :(

[@rodrigoeusebio7208]

My teacher uses imagens from your video to teach about telomers in molecular biology, great job.

[@shadawnhenderson9186]

THANK YOU FOR THIS!

[@iamsayemsarkar]

You are an Arab for sure. Most probably from Israel Institute of Technology.

[@Momo-ew3oi]

U deserve the world

[@hannahg5216]

Brewer thinks he’s got an extra stick of nucleotide on his 🧬 he’s gonna live 4ever. When that cap on the tip of the Telomeres disappear that is when a human begins to die, right? They fade over time much like cartilage in a knee. That last frame looks a heck of a lot like a gummy worm. Jus sayin.

[@sumansau418]

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.

[@guesswho1840]

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.

[@yashshroff3841]

I FINALLY get it

[@unalahmetakar7621]

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.

[@sagarboss2004]

Thanks so much

[@eningtu6291]

in 1983 telomeres have been a runing experiment by the buck institute of marin county ca. the discovery was publishe in a high school scolastic magazine, scientic weekly 1983. the tyrant that runs the buck intitute has under asault and threats of death, infact run me out of gainfull employment more thane once.

[@kipling1957]

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.

[@cozyandeasywinningwithlear6542]

1. Do the both ends of DNA have telomere sequence?? if both ends have telomere, how telomere is formed in daughter DNAs in 5' end of parent strand/ non-primer end of daughter strand/ 3' end of daughter strand? 2. Without telomerase, one end of both daughter DNAs get shortened or both ends?? if both ends get shortened, how parent 5' end get shortened??

[@oovajava6874]

It was helpful thanks for the video but please next time write and practice what you will be saying throughout the video because you are definitely not fluent in English as you speak quite badly and waiting for you to finally pronounce the word is super time consuming. Thank you for the information.

[@UHFStation1]

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.

[@ranim3082]

Thank you so much for this video, seriously I was so lost but this saved me before my exam😭❤️

[@xxxxyz854]

When it understood why the telomeres shorten a solution may be discoveted that is similar to the infinate replicating jellyfish that never dies can be available to wealthy humans, pets and political dictators.

[@kipling1957]

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.

[@hyderali692]

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?

[@chewerxian1260]

Sry to ask but what about the first primer in the leading strand? It will be removed eventually right? Does the leading strand gets shorter?

[@aaqibjavid5623]

isnt this problem happening with leading strand as u talk about only lagging strand

[@biomedicalandbiologicalsci4989]

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 ..

[@aaqibjavid5623]

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.

[@biomedicalandbiologicalsci4989]

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.

[@r.studio6170]

In chromosome..dna is wrapped around histones but when unwrapped and replicate..where histones go.please answer

[@jerrymdanowski9825]

What about fused Telomeres...Genetic Tampering ?

[@rotagbhd]

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.

[@vikramthimaradka97]

Title is misleading.Topic starts from 7:05 . How can the parent strand suddenly disappear like that and then u say the tip of the DNA is maintained!

[@naeem6749]

But the problem will be same for leading strand if you remove the first primer.....

[@austinadel8224]

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 ?

[@manasichavan4914]

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?

[@waelfarshoukh2294]

I want to tell you that the problem is on both strands. how the primer of the leading strand is replaced without any problems ??

[@kratinagrawal4078]

A very big thanks to u .....after half an hour waste....found u and now it's clear

[@Pilotamericano]

I don't understand where does the primer come from @9:56 and how does the completion happen afterwards?

[@leoniew1255]

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 🤯

[@mateuszcielas3362]

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?

[@OloladeGaniu-r9r]

Best explanation indeed Thanks for sharing

[@acetylcoa8559]

Leading strand doesn’t require primer to start elongation????

[@hanyelhag1664]

That was an awesome video and explanation ..I can say I fell in love with you hahaha BTW you pronounced " Synthesis" right at the beginning .. I don't know why you changed that XD Any how, thaank youuu sooo much and please keep up posting awesome videos like this ..!!

[@biomedicalandbiologicalsci4989]

Hany ElHag hahaha thank u for the nice comment... ya sure I will keep doing interesting videos so stay around... and I will look again for the pronunciation of synthesis .... BTW, if u have suggestions for other topics don't hesitate to tell me :)

[@ahmedhelmy8127]

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.

[@earthworm-filledstomachbyc4254]

Seek Christ Jesus YHVH God Almighty !

[@abdowagdy5787]

very thank you .. this explanation is so amazing > i want to ask about c rich & G rich

[@biomedicalandbiologicalsci4989]

Thank you for your comment .. what is your question about c rich and G rich regions?

[@abdowagdy5787]

Where are the position of C-rich & G-rich? How the overhanging occur ?

[@biomedicalandbiologicalsci4989]

If you are asking about C and G rich regions in the chrommosomes in general ... they can exist anywhere in the chromosome. However, the telomere is a G rich region it exists at the tip (very end) of the chromosome (13:22) ... overhangs occur every time there is a lagging strand shortening because of the end replication problem (7:00). The answers of your questions are all in the video :)

[@ricardochungus614]

this really simplified it for me, thank u so much

[@arjunp946]

Role of telomerease in cancer ? Can u please answer this in simple

[@Am-yo4hx]

can u explain how this causes heart,diabetes and cancer?

[@zainhamza49]

really helpful after watching 4 vids

[@shivankursharma2946]

Thanks very much That was really good

[@ASHTUTORIAL]

Finally after looking for so many videos...understood well....thanks a lot👌👌👍👍👍

[@Shobitmahajan]

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??

[@Kurikost_]

excellent question...i understand every aspect of this topic, but what is about the leading strand.

[@tehvenchien8893]

Thanks god I patiently watch till the end and finally get sth from u

[@zyleafpunch5684]

FUCK MY SCIENCE PROJECT, THIS SHIT IS TOO HARD

[@isabelrustler2330]

thank you so much now i wont fail my test tomorrow

[@ZenaBlbas]

Thanks very much I hope you continue

[@shkokurda2098]

Which gene encodes for telomerase in human?

[@chrisquarrie]

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.

[@hyderali692]

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.

[@dakaloratshivhombela8982]

Mahhhn! Well explained. Thanks.😋

[@blackwood5851]

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.

[@luciachp3519]

Thank u for making the video

[@muqiguo1453]

Many thanks! It is very helpful!!

[@dakaloratshivhombela8982]

Naahhhh!!!! I still love this videooo🤩🤩

[@argammargosian3278]

Thank u so much its really helpful

[@sivanissachar2508]

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?

[@Atahirysf-ud3vj]

It will connect with the one close to it i.e the second one so the bond is formed

[@آيةلعلهاتكونالشفاعة]

جميل جدا شكرا thank you

[@ilknur4142]

thank you... this is really good.

[@bharathreddy9337]

thanks a lot for explaining complex idea in simple manner. your diagrams are easy to visualize. beautiful

[@biomedicalandbiologicalsci4989]

Thank you :D

[@macedonia350]

Oh thank you very very very veryyy muuuuch!

[@dineshalove2902]

Thank youuuuuuuuu sssssoooooo much. 😘😘😘😘😘😘

[@habibamohshina1623]

Wow it was great..... Thank you..

[@mellenomweno2709]

I would recommend this video. it makes bio 221 concepts easy

[@biomedicalandbiologicalsci4989]

Thank you for your comment ..

[@umutkaratekin4662]

Thank you for explanation

[@tabimansour]

Amazing explanation, thank you ... I subscribed to this channel hoping to encourage you do more amazing videos like this.

[@hanansahl8896]

Thank u soon much Your explanation is so great If u donnot mind I wannaa to ask u some q , I am medical students and I am really in need to your help If u have telegram can u please give me the link and contact with me

[@RajeevKumar-es8be]

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

[@frankweinholt8787]

What about Cyclic Telomerase, the form of Telomerase that I believe (if my reading is current) is a variant that actually makes the (tumor) cell immortal. Doesn't Telomerase have something to activate them, if not, then why don't all cells that have telomerase stay immortal.

[@zakiyashahnaz4628]

The best explanation so far... I would not have understood it without this video... God bless the teacher

[@Abhinav-kf4wd]

Thank u so much. This is the best video on KZbin explaining the end replication problem and its solution by telomerase enzyme. Really very helpful video for students. God bless u !!

[@farheenayub8144]

this is very beautifully explained

[@tchoudjan]

Very interesting. So in the end replication, the parent DNA extension is cut off and disappears like the RNAs.

[@muhabrehman8645]

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?

[@poincareconjecture5651]

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:)

[@manijanazim]

DNA polymerase II ALWAYS add nucleotides from 5' to 3' - not the other way round.

[@chairwood]

so there is really no problem

[@muhammadnaushad3955]

Soled my problem tnkssss

[@MohitKashyap-bx9tz]

Excellent explanation mam

[@sincere995]

Very nice and neat explanation