1. New Approach to
Protecting Prion
from Altering and
'Cowcatcher'
Enzyme Fixes
Single-Strand DNA
Oscar Andrés Parra
Medicine student
III semester
UPB

2. MEDICAL UTILITY
First. This study puts us one step
closer to understand how
recently discovered prion caused
deseased work and what
treatment could be useful to
prevent or even cure this
deseases, incurable to the
moment
Second. DNA fixing mechanism
are of the most importance in the
process of
aging, neurodegenerative
deaseases and cancer, a better
understanding of the proteins
involved in genetic repairing is
important as a way to further
investigate why they fail at their
function causing DNA mutation
BIBLIOGRAPHY
• University of Texas Medical
Branch at Galveston (2013, July
29). 'Cowcatcher' enzyme fixes
single-strand
DNA. ScienceDaily. Retrieved
August 4, 2013, from
http://www.sciencedaily.com-/
releases/2013/07/130729161751.
htm
• Case Western Reserve
University (2013, July 18). New
approach to protecting prion
protein from altering
shape, becoming
infectious.ScienceDaily.
Retrieved August 4, 2013, from
http://www.sciencedaily.com-/
releases/2013/07/130718130454.
htm
FOLDING
New Approach to
Protecting Prion
from Altering and
'Cowcatcher'
Enzyme Fixes
Single-Strand DNA
MOLECULAR BIOLOGY
Oscar Andrés Parra
Medicine student
III semester
UPB
Teacher
Lina Maria Martínez Sánchez

3. INTRODUCTION
Prions are proteins with an altered
structure and a self-replicating
capacity, and are identified as the
cause of incurable and sometimes
transmisible diseases such as the
mad cow desease, very little it’s
known about the mechanism of these
prion deseasean recent studies on
how the alter normal proteins may
give us a clue for a succesful
treatment in the future
On the other Hand, DNA
Repairing Mechanisms are esential in
the comprehension of
neurodegenerative deseases, aging
mechanisms and cancer, finding a
new protein that participates in this
proces s can give us a better
understanding of why they fail and
how to avoid it
'Cowcatcher' Enzyme
Fixes Single-Strand DNA
Science daily July 29, 2013
Every time a cell divides it exposes its DNA
to great danger in the form of single
strands, this strands are particularly
vulnerable to reactive oxigen species that
may alter the information they contain. If
left unchecked this mutations can lead to
disorders linked to DNA damage such as
aging, neurodegenerative deseases and
cancer
UTMB scienists are working with an enzime
called NEIL 1 wich was previosuly known to
recognized single stranded DNA and was
asosiated with the replication
complex, through experiments he
researchers found that NEIL 1 actually rides
in front of the replication complex, scouting
for single-strand DNA damage and as soon
as it enconters a base damage, the site is
marked and replication stops, then the DNA
strands are allowed together again so the
damage can be repaired
Student Observation : as the article
stated, DNA damage its linked to a
various number of degenerative deseases
Adn comprehension of the repairing
mechanism its important to prevent
them from failing. NEIL 1 protein
function wasn’t really clear before this
investigation and from now on, knowing
its true purpose new investigations will
be focused on this protein
New Approach to
Protecting Prion Protein
from Altering Shape,
Becoming Infectious
Prion deseases include mad cow desease and
fatal failiar insomnia, unlike any other
transmisible deseases, prion deseases are
caused by an abnormal shaped prion protein
it is believed that they self-replicate by
binding to normal proteins produciong
another abnormal prion thus increasing their
numbers. A team of researchers from Case
Western Reserve University School of
Medicine have identified a mechanism that
can prevent the normal prion protein from
changing its molecular shape into the
abnormal form responsible for
neurodegenerative diseases.
The researchers generated a variant of prion
protein designed to stabilize the normal shape
of one specific part of the protein. They
accomplished this goal by replacing just one
out of more than 200 amino acid residues, the
building blocks of the protein. In a series of
experiments, the researchers found that the
modified prion protein was highly resistant to
changing its shape. In other words, this
approach may be successful in blocking the
coercive action of the abnormal prion protein.
Student observation: the result of this
research shows a promising start for a prion
desease prevention treatment or even a cure
of the existing desease, its a first step to
greater improvements in the little know field
of prion deseases

4. INTRODUCTION
Prions are proteins with an altered
structure and a self-replicating
capacity, and are identified as the the
cause of incurable and sometimes
transmisible diseases such as the
mad cow desease, very little it’s
known about the mechanism of these
prion deseasean recent studies on
how the alter normal proteins may
give us a clue for a succesful
treatment in the future
On the other Hand, DNA
Repairing Mechanisms are esentian
in the comprehension of
neurodegenerative deseases, aging
mechanisms and cancer, finding a
new protein that participates in this
proces s can give us a better
understanding of why they fail and
how to avoid it
.
researchers from Case Western Reserve University
School of Medicine have gone one step closer on the
comprehension of prion desease mechanisms by
identifying a mechanism that can prevent a normal
prion protein from changing to its abnormal
infecting form
New Approach to Protecting
Prion from Altering
UTMB scientists found out more about a protein
called NEIL 1 that was previously asociated with the
replication complex, they found out that NEIL1 scouts
for base errors before the the replication gets to that
point of the DNA strand, allowing it to be repaired
before continuing the replication
'Cowcatcher' Enzyme Fixes
Single-Strand DNA

5. 'Cowcatcher' Enzyme
Fixes Single-Strand DNA
Science daily July 29, 2013
Every time a cell divides it exposes its DNA
to great danger in the form of single
strands, this strands are particularly
vulnerable to reactive oxigen species that
may alter the information they contain. If
left unchecked this mutations can lead to
disorders linked to DNA damage such as
aging, neurodegenerative deseases and
cancer
UTMB scienists are working with an enzime
called NEIL 1 wich was previosuly known to
recognized single stranded DNA and was
asosiated with the replication
complex, through experiments he
researchers found that NEIL 1 actually rides
in front of the replication complex, scouting
for single-strand DNA damage and as soon
as it enconters a base damage, the site is
marked and replication stops, then the DNA
strands are allowed together again so the
damage can be repaired
Student Observation : as the article
stated, DNA damage its linked to a
various number of degenerative deseases
Adn comprehension of the repairing
mechanism its important to prevent
them from failing. NEIL 1 protein
function wasn’t really clear before this
investigation and from now on, knowing
its true purpose new investigations will
be focused on this protein

6. The researchers
at UTMB where
working on the
protein called NEIL 1
(cowcatcher)
This protein was
previously related to
the replication
complex
NEIL 1 role in the
replication was yet
unknown, until
now

7. Researchers found
that NEIL 1 rides in
front of the
replication complex
And scouts for DNA
damage
Then flags the
abnormal base and
stops replication
NEIL 1

8. • After replication stops the replication machinery
stalls and then regresses, and the two strands
come back together
• which allows repair of the damaged base in
duplex DNA
• by replacing the damaged base with the
appropriate normal base

9. Observation
DNA replication and repairing process is a lot more
complex than we usually see in the textbooks, the
discovery of the NEIL 1 function proves that, because
something that plays a mayor role in DNA error
checking and correction such as NEIL 1 was unknown to
the moment, that makes me think that there may be a
lot of other mechanisms that also are esential in DNA
replication that may not be yet found.

10. New Approach to
Protecting Prion Protein
from Altering Shape,
Becoming Infectious
Prion deseases include mad cow desease and
fatal failiar insomnia, unlike any other
transmisible deseases, prion deseases are
caused by an abnormal shaped prion protein
it is believed that they self-replicate by
binding to normal proteins produciong
another abnormal prion thus increasing their
numbers. A team of researchers from Case
Western Reserve University School of
Medicine have identified a mechanism that
can prevent the normal prion protein from
changing its molecular shape into the
abnormal form responsible for
neurodegenerative diseases.
The researchers generated a variant of prion
protein designed to stabilize the normal shape
of one specific part of the protein. They
accomplished this goal by replacing just one
out of more than 200 amino acid residues, the
building blocks of the protein. In a series of
experiments, the researchers found that the
modified prion protein was highly resistant to
changing its shape. In other words, this
approach may be successful in blocking the
coercive action of the abnormal prion protein.
Student observation: the result of this
research shows a promising start for a prion
desease prevention treatment or even a cure
of the existing desease, its a first step to
greater improvements in the little know field
of prion deseases
New #2

11. The mechanism
of abnormal
prion protein
Self replication
its not yet clear
The actual theory is that
prions replicate by altering
the structure of a normal
protein, producing a second
abnormal prion
Based on this theory the researchers
created a variant of prion protein
designed to stabilize the normal shape
of one specific part of a normal protein

12. The researchers found out that
the modified prion was highly
resistant to changing its shape
Showing that this approach may
be successful in blocking the
pathological action of the
abnormal prion protein
Then, they created transgenic
mice that produced the
stabilizer protein and infected
them with the mad cow
desease to see the outcome

13. The transgenic mice took almost twice the time
to show the signs og the desease han the normal
mice
Proving that the modified protein was
succesful in slowing down the desease
Giving at least a starting place to look for a cure
to a decease with no effective treatment to the
moment

14. Observation
One of the most interesting aspects of this new is that it
almost proves that the actual theory of prion protein
replication is correct, because the succes of this proyect was
based on the fact that prion proteins modified normal
proteins, making it useful to have a normal protein resistant to
the modification, if the mechanism is different, the
experiment would have not shown any difference between the
two mouse groups
Also it is a sustantialy important advance in the treatmente of
prion deceases, wich are incurable to the moment in humans

15. Medical Utility
As stated before, DNA repairing
mechanisms are esential to the
study of neurodegenerative
deceases such as alzheimer or
parkinson, in the understanding
of natural aging and the causes of
cancer. It is necesary to know the
reason of a pathology in order to
investigate for a better treatment

16. Medical Utility
There is a chance that some deceases related to
DNA damage are related to the abnormal
function of the NEIL 1 enzyme
specificaly, so, understanding its role in the
replication process may be of key value in future
investigation against DNA mutation derived
illness

17. Medical Utility
This investigation makes the
mechanism of prion deceases
spreading a lot clearer, since it has
been a mistery for medicine from the
moment it was discovered that
abnormal proteins could serve as
a transmissible decease, this can give
an starting point for treatment
investigations in the future

18. Medical Utility
The study proved effective against a prion that normaly
infects humans, causing the Creuzfeldt-Jakob disease , and
with no effective treatment to the moment it could be the
start of a brand new pharmacological strategy consisting of
creating molecules that can stabilize prion proteins in
order to prevent the propagation of the symptoms

19. Bibliography
• University of Texas Medical Branch at Galveston (2013,
July 29). 'Cowcatcher' enzyme fixes single-strand
DNA. ScienceDaily. Retrieved August 4, 2013, from
http://www.sciencedaily.com-/releases/2013/07/13072
9161751.htm
• Case Western Reserve University (2013, July 18). New
approach to protecting prion protein from altering
shape, becoming infectious.ScienceDaily. Retrieved
August 4, 2013, from
http://www.sciencedaily.com-/releases/2013/07/13071
8130454.htm

20. tThanks!