DNA replication involves copying genetic material to produce new DNA molecules. Errors can occur during this process due to DNA polymerase, the enzyme responsible for DNA replication. A new study tracked DNA polymerase enzymes and found they can leave behind scaffolding sections during replication that contain errors. These scaffolds become trapped in regulatory regions of DNA and can lead to genetic diseases and cancer by altering important genetic switches. Understanding where errors occur provides insight into disease development and could help researchers develop more targeted treatments.

1. Genetic errors due to
DNA polymerase
Amelia Molina Moreno
Medicine Student 3rd semester

4. DNA CONTAINS ALL
OF OUR GENETIC
INFORMATION
• IN ORDER FOR IT TO
HAVE IT COMPLETE
IT MUST SUFFER A
REPLICATION
SEMICONCERVATIVE
The REPLICATION is the process of the DNA were he copies in order to be transmited,
in this proces it obtaines two molecules of daughter DNA formed by a original fork and a
new fork.
. .

5. The diference that researcher has found with other cancers is that
children with this syndrome develop more mutations than any human
cancers by far (20,000 mutations in six months) .
'biallelic mismatch repair
deficiency' (bMMRD)
But this little step
is the responsible
of several
syndromes
WHICH CAUSES:
1. multiple brain tumors
2. Lymphomas
3. gastrointestinal cancers by the age of 10

6. “Ultimately, we hope this
leads to treatments to avoid
the presently inevitable
consequences of this
predisposition syndrome”
• One of the biggest problems this kids have is
that they dont count with an specific treatment,
becouse scientist create treatments for more
common cancers.
This study will help the scientist so they
could do more targeted treatments and will
be a huge advanzed for prevention of
cancer

7. • This study identifies a secondary
mutation which occurs only in
tumor cells in an enzyme called
polymerase, which is a second
safeguard that helps to effectively
repair mutations while the DNA
replicates.
• The combination of these two
mutations leaves patients with
no ability to repair mistakes that
may occur while DNA is
replicating, and causes a rapid
wave of cancer that the
investigators have dubbed the
"great flood."

8. • This has important implications
for both diagnosis and targeted
treatment of this devastating
disease
• This study provides a major step forwards in
understanding why certain children are more
susceptible to developing multiple cancers.
• Allows us to
understand the
steps that lead
to cancer
developing
• Our findings indicate the genetic driver that
causes this 'great flood' of cancer mutations in
patients with bMMRD. The secondary mutation
in the enzyme polymerase causes a unique
signature of mutations that is present in 100 per
cent of the cases.

9. “We were able to describe how many mutations develop, how
fast they occur, how many mutations the tumor can sustain, and
the type of mutation that occurs, which we found is unique to
bMMRD cancers"
• The biggest goal achieve during
this study was to take a deeper
look at this cancer predisposition
syndrome and for the first time
they are able to tell the story of
how this cancer develops.
HOW?
The Children's Brain Tumour
Research, Using genetic and
clinical information and tumour
samples gathered from each
patient.

10. THIS NOT ONLY MEANS AN ADVANZED ON
DIAGNOSIS AND TREATMENT IT ALSO HELPS
SCIENTIS TO UNDERTAND THE STEPS IT TAKES TO
DEVELOPE CANCER IN GENERAL.
• Because the high number of mutations
is so specific to bMMRD syndrome,
researchers are able to detect children
who are carriers just by sequencing the
tumor.
• "If the child has a very high number of
mutations then we know immediately
that they have this cancer
predisposition syndrome,"
NEW
LIGHT

11. HOW NATURALLY
OCCUR MUTATIONS
IN OUR DNA?

12. University of Edinburgh researchers developed a method to label -- and
track -- pieces of new DNA as they are made and to identify which
copying enzyme is responsible.
The study of how DNA replicates has shown how it change over time
and how our genome has been shaped over evolution and has revealed
that some of the genetic switches that control when genes are activated
are likely to be hotspots for DNA flaws, or mutations, to develop.
One of the
multiple
causes are
Copying
enzimes

13. One of the most important is the Polymerase
• One polymerase first
makes short stretches
of DNA that act as a
scaffold so that the
other copying enzymes
can then replicate the
remaining DNA.
• As this scaffold DNA
contains errors, the standard
model assumed all of it was
removed during the process
• These scaffold sections,
and the mistakes they
contain, become
trapped in the DNA.

14. WHY?
• This often ocurrs at points in the important regulatory
switches. These sites are therefore more likely than other
regions to have trapped scaffold DNA and its associated
errors.
• Mistakes in these crucial step of genetic sequences can
change or destroy the regulatory switch, which can lead
1. To genetic disease
2. Alter susceptibility to common diseases
3. Contribute to the development of cancer.

15. The new goal of
researchers?
• That this new achieve helps understanding why mutations happen
and more complete to see these in regions were it doesnt codify
for proteins.
• If the scientists could find the cause of why the DNA is unable to
identify the error and repare it, we could be talking about a new
light of treatments using as a target the DNA Polymerase

16. “We have been aware of striking patterns in
how DNA changes for several years but
couldn't explain why the patterns were there”
This study gives:
1. mechanism and revealed
previously unseen patterns
2. Point to sites in our DNA that
are likely to have a high rate
of damaging mutations.
If scientist focus in those
points were damaging
mutations are most likely to
occur they they can create
treatments more specific
and not so common for al
cancers o genetic diseases.

17. WHATS NEW?
• Groups of scientist have created a new
method to track polymerase enzymes that
copy our genome.
• This shows us that despite DNA replication
is an amazingly accurate process, errors do
occur and most of all in very important
parts of our genome
Our genome has also been
part of evolution, during it
our genome has been
shaped into our needs but
also giving space to new
mutations never seen
before.

18. • But the questions will be
1. Why the process that is in charge of controling flaws in
the DNA replication is unable to recognize all of them ?
2. Why some people are more suceptible for mutations?
Those are answers that our advanced medicine and
technology are searching for

19. In conclusion…
Error
DNA
Regulation
point
doesnt
detect the
error
Polymerase
replicates
A MUTATION IS NOW IN THE DAUGHTER DNA

20. Observations
1. When we know and understand how our DNA replicates it help us to
understand how our genome has been change over the evolution even more
it help us to see were the most common errors occur and to see specifically
which enzyme is the responsible for the mutation
2. Medicine is getting to see which are the steps that’s the cancer does to
develop also they could diagnosis before we are born and create treatments
more specific for those kids who are more susceptible to multiple cancers