1. Enzyme Reverses Stalled Transcription
Machinery to Aid DNA Repair
AND
Myotonic Dystrophy Disrupts Normal
Control of Gene Expression in Heart.
Maria Isabel Perez Palacio
UPB School of Medicine
Third Semester
2014

4. • Scientists have been working on
different experiments that focus on the
origins of disease, this implies the use of
techniques involving DNA.
• Researchers discovered an enzyme
responsible for “scanning DNA” , this is
a method of DNA reparation.
• The relationships between expressed
genes and other factors such as
microRNA have profound effects on
specific
diseases
like
myotonic
dystrophy, this can be the possible cause
of its many varied symptoms.

5. Enzyme Reverses Stalled Transcription
Machinery to Aid DNA Repair
•
Researchers from NYU
Langone Medical Center
held an experiment on
DNA in E.coli
•
RNA polymerase plays
an essential role in
excision repair
•
Discovery of UvrD
enzyme in E.coli allows
for mechanism known
as backtracking.

6. Enzyme Reverses Stalled
Transcription Machinery to
Aid DNA Repair
•
RNA polymerase is snagged by
faulty DNA causing it to pull
backwards to expose the sequence,
allowing for the reparation of the
error.
•
The UvrD enzyme binds to the RNA
polymerase and facilitates the
repair.
•
The researechers also noted that
NusA has an elongation effect that
cooperates with UvrD
• “Both promote backtracking
and recruiting nucleotide
excision repair enzymes to
exposed lesions. ”

7. Enzyme Reverses Stalled Transcription
Machinery to Aid DNA Repair
• Humans have similar repair mechanisms, involving a protein XPB
• This has a relationship with diseases such as xeroderma
pigmentosum, Cockayne syndrome, and trichothiodystrophy
• This repair mode means slower aging, less cancer and other diseases.
• This is the only molecular machine that continuously scans
chromosomes for any irregularities in the DNA.

8. WHY DOES THIS HAPPEN ?
• Scientists wondered: Why do RNA polymerases transcribe most of
the genome when only a small fraction of it will be useful?
▫ The research proved that the reason why RNA polymerases work
continuously is to patrol the genome and avoid transcribing
mutations.

9. STUDENT’S OPINION
• This type of research is extremely valuable, especially to
health professionals because if scientists are able to
utilize this new mechanism of gene repair to be able to
control the expression of genes such as XPB then we can
halt the expression of these diseases or find the mutation
before hand and eventually cure them.

10. Myotonic dystrophy disrupts normal control
of gene expression in heart
• The research was
conducted in the
Baylor College of
Medicine
• The tests were
executed on mice
and human heart
tissue
• They focused on
the actions of
microRNA in
myotonic
dystrophy.

11. Myotonic dystrophy
disrupts normal control of
gene expression in heart
•
Myotonic dystrophy type 1
causes a disruption in the
transcription network
controlled by MEF2 located in
heart tissue
•
The number one cause of death
of this disease is the heart’s
inability to beat properly.
•
In myotonic dystrophy ,
microRNA are affected
•
microRNA are responsible for
the “fine tuning” of protein
expression.

12. Myotonic dystrophy disrupts
normal control of gene
expression in heart
•
Myotonic dystrophy occurs because
the gene DMPK is abnormally
duplicated.
•
This study shows that not only
messenger RNA are affected but also
microRNA (genetic actors)
•
During the study 500 microRNAs
were scanned and 54 were found
affected.
•
A study on human heart tissue
showed 20 of these were down
regulated in myotonic dystrophy
SIX5
gene
CTG
repeat
Termination
codon
DMWD
gene

13. Myotonic dystrophy disrupts
normal control of gene
expression in heart
•
microRNAs are genetic actors
that take the genetic code to the
part of the cell where proteins
are assembled.
•
MEF2 is a transcription factor
that affects microRNA as well as
the activity of other genes.
•
Gene regulation is dynamic and
changes with different
conditions, however in this
diseases the abnormality in
MEF2 causes multiple
damaging effects.

14. STUDENT’S OPINION
• The discovery of the involvement of microRNA is
important because now there can be a study focused on
the abnormal expression of these proteins and therefore
help have some control over the symptoms implicated in
this disease, it could serve as a way to minimize the
secondary symptoms, like a therapy although it wouldn't
help to cure the disease. Hopefully helping better the
quality of life of these patients.

15. MEDICAL UTILITY
• Both investigations offer
important insight into the
origins of different diseases that
affect people all over the world
• Being able to understand
illnesses from a molecular point
of view can help us to eradicate it
from its origin.

16. MEDICAL UTILITY
• Investigating gene repair at its origin by utilizing RNA
polymerase, UvrD, and XPB can help maintain a healthy
genome and avoid the replication of DNA with unique
mutations that cause genetic diseases like xeroderma
pigmentosum amongst others.

17. MEDICAL UTILITY
•
Researching into the genetic
effects that cause the various
symptoms of diseases such as
myotonic dystrophy can help
to better understand the
illness and therefore create
treatment therapies for these
patients
that
focus
on
generating some relief , if
curating is not an option.

18. MEDICAL UTILITY
• Medically its useful to explore genetics and find search
for the underlying causes of diseases because we can get
closer to finding a cure and being able to help people
suffering from these ailments fell better, live longer and
we can offer them a better quality of life.

19. BIBLIOGRAPHY
•sciencedaily.com [Internet]. Texas: Bayor College of
Medicine; 2014. [updated 9 January 2014; cited 22
February 2014]. Available from:
http://www.sciencedaily.com/releases/2014/01/14010913
2313.htm
•genengnews.com [Internet]. New York: NYU Langone
Medical Center; 2014. [updated 9 January 2014; cited 22
February 2014]. Available from:
://www.genengnews.com/gen-news-highlights/enzymereverses-stalled-transcription-machinery-to-aid-dnarepair/81249345