New Approach to Protecting Prion from Altering and 'Cowcatcher' Enzyme Fixes Single-Strand DNAOscar Andrés ParraMedicine studentIII semesterUPB

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

UPBTeacher

Lina Maria Martínez Sánchez

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, DNARepairing 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 repairedStudent Observation : as the article stated, DNA damage its linked to a various number of degenerative deseasesAdn 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 InfectiousPrion 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

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, DNARepairing 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

NEW #1

'Cowcatcher' Enzyme Fixes Single-Strand DNA

Science daily. July 29, 2013

'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 repairedStudent Observation : as the article stated, DNA damage its linked to a various number of degenerative deseasesAdn 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

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

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

• 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

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.

New Approach to Protecting Prion Protein from Altering Shape, Becoming InfectiousScience daily. July 18 2013

New Approach to Protecting Prion Protein from Altering Shape, Becoming InfectiousPrion 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

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

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

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

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

Medical Utility

'Cowcatcher' Enzyme Fixes Single-Strand DNA

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

Medical Utility

'Cowcatcher' Enzyme Fixes Single-Strand DNA

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

Medical Utility

New Approach to Protecting Prion Protein from Altering Shape, Becoming Infectious

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

Medical Utility

New Approach to Protecting Prion Protein from Altering Shape, Becoming Infectious

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

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

tThanks!