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Replication Errors

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231 views

Replication Errors

Uploaded by

ilkay turan
Copyright
© © All Rights Reserved
Available Formats
Download as KEY, PDF, TXT or read online on Scribd
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Replication Errors

Learning Outcomes

Structure of DNA
Structure of Replication
Replication Errors
Fixing mechanisms
DNA Structure
DNA exists as a double-stranded structure, with both strands wrapped
together to form the characteristic double helix. Each single strand of DNA
is a chain of four types of nucleotides. Nucleotides in DNA contain a
deoxyribose sugar, a phosphate, and a nucleobase. The four types of
nucleotide referred to the four nucleobases adenine, cytosine, guanine, and
thymine, commonly shorten as A, C, G, and T. Adenine and guanine are purine
bases, while cytosine and thymine are pyrimidines. These nucleotides form
phosphodiester bonds .Nucleobases are matched between strands through
hydrogen bonds to form base pairs. Adenine pairs with thymine (two
hydrogen bonds), and guanine pairs with cytosine (three hydrogen bonds).
DNA strands have a directionality, and the
different ends of a single strand are called the "3 ′
end and the "5′ end. By convention, if the base
sequence of a single strand of DNA is given, the
left end of the sequence is the 5 ′ end, while the
right end of the sequence is the 3 ′ end. The
strands of the double helix are antiparallel, with
one being 5′ to 3′, and the opposite strand 3 ′ to 5 ′.
These terms refer to the carbon atom in
deoxyribose to which the next phosphate in the
chain attaches. Directionality has consequences
in DNA synthesis, because DNA polymerase can
synthesize DNA in only one direction by adding
nucleotides to the 3′ end of a DNA strand.
DNA Replication:

It is extremely important that all cells resulting from the division


of a cell receive an identical copy of DNA. This process of
making copies occurs through replication and occurs once in
the life cycle of each cell. DNA replication occurs before cell
division, during the S phase of interphase. The fact that the two
strands in DNA are complementary to each other shows that
when one strand is known, the other strand can also be created.
The weak hydrogen bonds connecting the arms of the helix open
like a zipper; In both arms, it leaves the purine and pyrimidine
ends exposed, which are separated from their partners.
As the two arms open , self-replication begins
when they come across the appropriate bases
in the arms. When the double helix of DNA is
separated from each other, as a rule, the
Adenine group combines with the Thymine
group and the Guanine group combines with
the Cytosine group and takes their place.
Others are turned away because they don't fit.
When all the nucleotides are paired, a new
chain is formed and the DNA replicates itself.
During DNA replication, the two strands
that make up the double helix each serve
as a template from which new strands are
copied. This process is semi-conservative
replication. When two copies of DNA are
formed in this way, they have the same
nucleotide sequence and divide equally into
two daughter cells.

The new copied DNA strands are exactly


the same, but occasionally the copying is
not perfect due to errors in replication.
Semi-conservative DNA model. The main
strands are shown in gray colors, and the
newly synthesized DNA is shown in blue
colors.
Replication Errors
While most DNA replicates with fairly high fidelity, mistakes do happen,
with polymerase enzymes sometimes adding the wrong nucleotide or too
many or too few nucleotides into a sequence. Fortunately, most of these
mistakes are fixed through various DNA repair processes. Repair enzymes
recognize structural imperfections between improperly paired nucleotides,
cutting out the wrong ones and putting the right ones in their place.

But some replication errors make it past


these mechanisms, thus becoming
permanent mutations. These altered
nucleotide sequences can then be passed
down from one cellular generation to the
next, and if they occur in cells that give rise
to gametes, they can even be transmitted to
subsequent organismal generations.
Today, scientists suspect that most DNA replication errors are
caused by mispairings of a different nature: non tautomeric
chemical forms of bases ( bases with an extra proton, which
can still bind but often with a mismatched nucleotide, such as
an A with a G instead of a T) or between "normal" bases that
nonetheless bond inappropriately because of a slight shift in
position of the nucleotides in space. This type of mispairing is
known as wobble. It occurs because the DNA double helix is
flexible and able to accommodate slightly misshapen
pairings.
Replication errors can also involve
insertions or deletions of
nucleotide bases that occur during
a process called strand slippage.
Sometimes, a newly synthesized
strand loops out a bit, resulting in
the addition of an extra nucleotide
base. Other times, the template
strand loops out a bit, resulting in
the omission, or deletion, of a
nucleotide base in the newly
synthesized strand. Regions of DNA
containing many copies of small
repeated sequences are
particularly prone to this type of
error.
Fixing Errors In Replication
Fortunately, cells have evolved highly sophisticated means of fixing most, but not all, of those
mistakes. Some of the mistakes are corrected immediately during replication through a
process known as proofreading, and some are corrected after replication in a process called
mismatch repair. When an incorrect nucleotide is added to the growing strand, replication is
stalled ,During proofreading, DNA polymerase enzymes recognize this and replace the
incorrectly inserted nucleotide so that replication can continue. Proofreading fixes about 99%
of these types of errors, but that's still not good enough for normal cell functioning.

After replication, mismatch repair reduces the final error rate even further. Incorrectly paired
nucleotides cause deformities in the secondary structure of the final DNA molecule. During
mismatch repair, enzymes recognize and fix these deformities by removing the incorrectly
paired nucleotide and replacing it with the correct nucleotide.
Incorrectly paired nucleotides that still remain following mismatch repair become
permanent mutations after the next cell division. This is because once such mistakes
are established, the cell no longer recognizes them as errors. Consider the case of
wobble-induced replication errors. When these mistakes are not corrected, the
incorrectly sequenced DNA strand serves as a template for future replication events,
causing all the base-pairings thereafter to be wrong. For instance, the original strand
had a C-G pair; then, during replication, cytosine (C) is incorrectly matched to adenine
(A) because of wobble. In this example, wobble occurs because A has an extra
hydrogen atom. In the next round of cell division, the double strand with the C-A pairing
would separate during replication, each strand serving as a template for synthesis of a
new DNA molecule. At that particular spot, C would pair with G, forming a double helix
with the same sequence as its original (i.e., before the wobble occurred), but A would
pair with T, forming a new DNA molecule with an A-T pair in place of the original C-G
pair. This type of mutation is known as a base, or base-pair, substitution. Base
substitutions involving replacement of one purine for another or one pyrimidine for
another (e.g., a mismatched A-A pair, instead of A-T) are known as transitions; the
replacement of a purine by a pyrimidine, or vice versa, is called a transversion.
Most replication mutations can also be caused by
various environmentally and spontaneous changes to
DNA. As with replication errors, most environmentally
DNA damage is repaired, which is chemically triggered
and causes a low rate of conversion to truly permanent
mutations .The same is true of so-called spontaneous
mutations. They are usually caused by normal chemical
reactions that go on in cells.most of these spontaneous
errors are corrected by DNA repair processes. But if
this does not occur, a nucleotide that is added to the
newly synthesized strand can become a permanent
mutation.
Finally ,of course not all mutations are "bad." But, because so
many mutations can cause cancer, DNA repair is obviously a
crucially important property of eukaryotic cells. However, too
much of a good thing can be dangerous. If DNA repair were
perfect and no mutations ever accumulated, there would be no
genetic variation and this variation serves as the raw material
for evolution. Successful organisms have thus evolved the
means to repair their DNA efficiently but not too efficiently,
leaving just enough genetic variability for evolution to continue.
References
https://evrimagaci.org/dna-hasari-ve-onarimi-hata-yapan-dna-parcalari-nasil-tamir-
edilir-11223
https://dev.mysql.com/doc/mysql-replication-excerpt/5.7/en/replication-features
-errors.html
https://www.nature.com/scitable/topicpage/dna-replication-and-causes-of-muta
tion-409/

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