The document summarizes the end replication problem faced during DNA replication in linear chromosomes. It discusses how the lagging strand cannot be fully replicated due to the absence of an RNA primer. It then describes two main solutions to this problem - protein priming in some bacteria and viruses, and the use of telomeres and telomerase in eukaryotes. Telomerase extends the 3' end of chromosomes to provide a template for complete replication.

1. REPLICATION OF
CHROMOSOMAL ENDS
By.
Vishal Panchal, 4609
Microbiology Department
Swami Shraddhanand College, University of Delhi

2. INTRODUCTION

4. END REPLICATION PROBLEM
▪ The requirement for an RNA primer to initiate all new DNA
synthesis creates a dilemma for the replication of ends of linear
chromosome, called the end replication problem.
▪ Seen in the lagging strand of the newly synthesised DNA after
the removal of the last RNA primer at the 5' end.
▪ Gap is created and new nucleotides cannot be added here since
no 3'-OH present here and not enough template for the primase
to add a new RNA primer for synthesis.
▪ Results in the shortening of DNA, which may result in loss of
some important genes.

7.  This problem is not faced by prokaryotes
having a covalently closed circular
DNA(cccDNA).
 The leading strand can simply continue to
grow 5' 3' until its 3' end is joined to the 5'
end of the lagging strand coming around in
the other direction.
 For the lagging strand, the replacement for
the RNA primer of the last Okazaki
fragment can be added to the free 3' OH
end of the leading strand coming around in
the opposite direction. Source: https://www.embibe.com/study/t
heta-model-of-replication-concept

8. How is this problem solved?

9. Solution for this end replication
problem
Protein Priming
▪ Priming protein binds to the
lagging strand template and
uses an amino acid(tyrosine)
to provide an OH that
replaces the 3'-OH normally
provided by an RNA primer.
▪ Examples : certain species of
bacteria and at the ends
of the linear chromosomes of
certain bacterial and animal
viruses.
Telomeres andTelomerase
▪ Telomere is a unique
structure that acts as a novel
origin of repliation that
compensates for the end
replication problem by
recruiting a specialized DNA
polymerase called
Telomerase.

10. TELOMERES
▪ The ends of chromosomes.
▪ Composed of head-to-tail repeats of aTG-rich DNA sequence.
▪ Protect chromosomes from degradation.
▪ Regulate telomerase activity at chromosome ends.
▪ Essential for chromosome stability.
▪ In humans telomere sequence is 5'-TTAGGG-3'.
▪ Not present in prokaryotes.

11. Illustration of a telomere
Creator: ttsz | Credit: Getty
Images/iStockphoto
Copyright: ttsz
Source: https://medicalxpre
ss.com/news/2017-03-link-
telomere-length-
cancer.html
Click to add text

12. TELOMERASE
▪ Found usually in germ cells.
▪ Includes multiple protein subunits and an RNA component
(ribonucleoprotien or ribozyme).
▪ Acts to extend telomeric sequence at the 3' end of its DNA
substrate/chromosome.
▪ Does not need an exogenous DNA template.
▪ Newly synthesized DNA(extended telomeric DNA) is single-
stranded.

13. Important Components or factors of
Telomerase
Telomerase RNA (TER)
▪ RNA component of enzyme.
▪ Varies in size from 150-3000 bases
depending on the organism.
▪ Includes a short region
that encodes about 1.5 copies
of the complement of the
telomere sequence and act as
template.
▪ For humans this sequence is 5'-
AAUCCCAAUC-3'
Telomerase ReverseTranscriptase
(TERT)
▪ Member of class of DNA
polymerases called "reverse
trancriptases".
▪ "reverse transcribes" RNA into
DNA.
▪ Synthesizes DNA to the end of
theTER template region.

16. Telomerase solves the end replication problem
by extending the 3'end of the chromosome
which provides an additional template for the
lagging-strand replication machinery to work.

17. TELOMERE-BINDING PROTEINS
▪ Two major functions
– Regulates telomerase activity and telomere length.
– Protects Chromosome ends.

18. ▪ Telomere length
regulation by telomere
binding proteins.

19. Telomeres form a looped structure in the cell called t-loop.

20. What happens to the cells without telomerase?
§ Telomeres gets shorter and shorter with each cell division.
§ If a cell divides enough times, the telomeres are in danger
of disappearing entirely, and the cell would then be at risk
of eroding its coding DNA.
§ This potential danger is averted by a cell destruction
pathway, known as Apoptosis(programmed cell death).

21. Aging, Cancer, and The Telomere Hypothesis
▪ The length of telomeric DNA limits the number of times a cell
could divide.This hypothesis supports the idea that telomeres
are connected to the cellular aging.
▪ For the hypothesis to be viable, normal cells should have little
or no telomerase activity.
▪ Cancer cells in culture indicates that they can divide indefinitely
(high proliferative capacity).This suggested that they have high
telomerase activity.
▪ There are numerous efforts seeking telomerase inhibitors as
chemotherapeutic agents.

22. REFERENCES
▪ James D.Watson. Molecular Biology OfThe Gene. 7TH Edition.
©2014 by Pearson Education, Inc. Chapter 9 Replication of DNA.
▪ Jeff Hardin, Gregory Bertoni, Lewis J. Kleinsmith. Becker's World
OfThe Cell. 8TH Edition. ©2012 by Pearson Education,
Inc. Chapter 19The Cell Cycle, DNA Replication, and Mitosis.