Enzyme Reverses Stalled Transcription Machinery to Aid DNA

Repair AND

Myotonic Dystrophy Disrupts Normal Control of Gene Expression

in Heart.  

Maria Isabel Perez PalacioUPB School of MedicineThird Semester2014

• 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.

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.

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. ”

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.

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.

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.

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.

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.

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

CTG repeat Termination

codon

DMWD gene

SIX5 gene

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.

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.

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.

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.

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.

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.

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/2014/01/140109132313.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/enzyme-reverses-stalled-transcription-machinery-to-aid-dna-repair/81249345