As we all know, with a linear chromosome, on the lagging strand (template 5'->3') of DNA replication, when the last piece of RNA primer at the 3' end is removed, the DNA cannot be extended and this creates the end replication problem.
My question is, on the leading strand (template 3'->5'), we also need a primer at the 3' end of the template to initiate the replication as it provides the free 3'-OH group for DNA pol to extend. If this primer is somewhere within the DNA, then its fine because it will eventually be filled by DNA pol coming from the leading strand of the previous replication fork. But if the primer is at the very end, when this primer is removed, how is the cell going to extend this bit of DNA? There is no 3'-OH to extend. and after each cycle, this will be shortened and just the same as the lagging strand, the leading strand should also suffer from the end replication problem as well. But people usually say only the lagging strand.
Thank you very much.
The replication origin is unlikely to be at the very end of the chromosome. Therefore, the end of the leading strand is most likely to be covered, which leaves the lagging strand to be the only problem, ideally.
Dear Anh
Nice question! As you mentioned, primers selection criteria are:
- Primer length
- melting temperature (Tm)
- Specificity
- Complementary primer sequences
- G/C content
- 3’-end sequence
But in PCR process, only the exact part of DNA is replicated. Your question is about the end part of chromosome in cell! These parts are called telomerase sites and their replication are a little bit different. I can’t give you more information because I am not expert in this field, but I hope my answer give you a clue.
Good luck
Hi Marzieh,
My question wasnt about PCR, its about the actual molecular mechanism in the cell!
I wonder after seeing your question. I was having the same question when I first read the DNA replication in eukaryotes in detail. There is a mechanism for this. Telomere End replication.Refer them:
https://www.boundless.com/biology/textbooks/boundless-biology-textbook/dna-structure-and-function-14/dna-replication-in-eukaryotes-103/telomere-replication-438-11663/
https://www.youtube.com/watch?v=AJNoTmWsE0s
The replication origin is unlikely to be at the very end of the chromosome. Therefore, the end of the leading strand is most likely to be covered, which leaves the lagging strand to be the only problem, ideally.
Yinbo Zhang: Very interesting! I think your answer is the most appropriate to explain this question. Thank you very much!
How I understand this is that replication will occur bidirectionally from the the origin inside the replication bubble. If we focus just on 1 parent strand being replicated, on one side of the origin, the daughter stand replication will be continuous. However, on the other side of the same daughter strand, the replication will require Okazaki fragments.
So for the same daughter strand, on one side of the replication origin, it will be leading, and on the other side of the origin it will be lagging!
Back to the telomere shortening (end replication problem), this will mean that each daughter strand will ONLY end up too short on their 5' end after the RNA primer (Okazaki fragment) is removed.
Dear Anh huang le,
please see the attached article, which is the best explanation for end replication problem concept. i hope, it is helpful to you
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