Navigation Links
Mount Sinai researchers find structural basis for incidence of skin cancers in a genetic disorder
Date:6/23/2010

Researchers from Mount Sinai School of Medicine have found why patients with a variant form of xeroderma pigmentosum (XPV), an inherited genetic disorder characterized by extreme sensitivity to the sun, are more susceptible to skin cancers than the general population. The data are published in the current issue of the journal Nature. Their finding sets the stage for research into therapies that would help protect people with XPV from developing skin cancers.

The research team determined that, in the general population, DNA polymerase eta, an enzyme able to overcome the barriers created by sun damage and ultraviolet rays and continue replicating DNA strands, is structured differently from any other polymerase. However, in people with XPV, since this enzyme is missing, they are unable to bypass this damage, causing the replication process to stall, resulting in mutations and extremely high susceptibility to skin cancer.

Researchers have never been able to fully determine a structural basis for why the enzyme can get around UV damage. After nearly a decade of research, the Mount Sinai team successfully developed a crystal model, or a three dimensional chemical derivation, of the enzyme. They determined that in the general population, DNA polymerase eta suppresses skin cancer because the active site, where chemical reactions required to replicate DNA take place, can adjust much better to UV damage than any other DNA polymerase.

"We have been unable to study how DNA polymerase eta can replicate through UV damage because we did not have a crystal structure of the enzyme to study," said Aneel K. Aggarwal, Ph.D, Professor, Structural and Chemical Biology, Mount Sinai School of Medicine. "Our team succeeded in developing this structure and determining what makes this enzyme unique."

In conjunction with Drs. Louise and Satya Prakash's group at the University of Texas Medical Branch in Galveston, Texas, Dr. Aggarwal's team generated crystals and analyzed them using X-rays. They determined that the active site of DNA polymerase eta is structured in such a way that it can easily accommodate the UV induced DNA lesions and replicate through them.

"Now that we know the structural basis for the suppression of skin cancers by this enzyme, one question for the future is if there's a way to restore its function in people with XPV and reduce their risk for cancer," said Dr. Aggarwal.

According to the National Center for Biotechnology Information of the National Institutes of Health, xeroderma pigmentosum is an inherited genetic disorder characterized by severe sun sensitivity resulting in blisters and precancerous freckles, benign tumors on the skin and eyes, blurry vision and eye pain from atrophic eye lids, and neurologic symptoms including cognitive decline.


'/>"/>

Contact: Mount Sinai Press Office
newsnow@mountsinai.org
212-241-9200
The Mount Sinai Hospital / Mount Sinai School of Medicine
Source:Eurekalert

Related medicine news :

1. Mount Sinai finds prenatal exposure to certain chemicals affects childhood neurodevelopment
2. Flat Screen TV Stands, TV Mounting Brackets and More: New Site, New Sale, Free Shipping
3. Mountain Home Experiences a Huge Response to Their Ground Breaking Free Lean Six Sigma Certification Offer
4. UniCare, Walmart Organize Circle of Hope To Help Mountain Mission Meet Increased Demand for Assistance
5. American Council on Exercise (ACE) Study Reveals Kettlebells Provide Powerful Workout in Short Amount of Time
6. Childhood obesity: Its not the amount of TV, its the number of junk food commercials
7. New York and Connecticut Drug Rehab Center Mountainside Weighs In on Latest White House Budget
8. Mountain Home 'Doing the Right Thing Really is the Best Business Approach'
9. Dominos Pizza(R) Raises Record Amount for St. Jude Childrens Research Hospital
10. Excitement Surrounding "Unveil Your Pink" Mounts!
11. Connecticut Governor Jodi Rell Honors Mountainside Addiction Treatment Center for its Twelve Years of Operating in Connecticut
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:5/24/2016)... , ... May 24, 2016 , ... ... physical disease or injury that focuses on repairing the musculoskeletal and neuromuscular systems ... an emphasis on functional restoration, NYDNRehab began providing treatments for physical therapy in ...
(Date:5/24/2016)... ... May 24, 2016 , ... A newly released report reveals that ... access to trusted resources, both in face-to-face interactions and online. In “Heard, Not Judged ... concluded that the creative use of mobile digital devices can be an effective tool ...
(Date:5/24/2016)... ... May 24, 2016 , ... The Radiosurgery Society (RSS), ... radiosurgery, is recognizing five medical residents and students for their outstanding contributions to ... The awards will be presented at the 2016 SRS/SBRT Scientific Meeting taking place ...
(Date:5/24/2016)... ... May 24, 2016 , ... Tuesday, May 24, Women's Excellence in ... enhanced with Young Living Essential Oils, taught by Patti Dolan, RYT, a Young ... location. Yoga Flow is 6:30pm - 7:15pm followed by a small intro to the ...
(Date:5/24/2016)... ... May 24, 2016 , ... WaterAid launched the #perioddrama campaign to mark ... than 1 billion women around the world who do not have access to a toilet, ... the US about their dread of #perioddrama. The (sometimes hilarious) results help shine a light ...
Breaking Medicine News(10 mins):
(Date:5/24/2016)... 2016 Cirujanos holandeses han puesto ... los médicos a compartir sus mejores prácticas por el ... Profesionales médicos de Europa, África, Asia ... la aplicación, que combina la transmisión en vivo con ... Educación   "Imagine un médico de ...
(Date:5/24/2016)... -- ARANZ Medical  Ltd a specialist in ... been named the Coretex Hi-Tech Emerging Company of the Year ... Bruce Davey , CEO of ARANZ Medical says, "This ... to be recognised for the work we are doing to ... 35 countries around the world from Sub-Saharan Africa through to ...
(Date:5/24/2016)... HONG KONG , May 24, 2016 ... , the world , s ... and AV fistula intervention   OrbusNeich, a ... solutions, has expanded its portfolio to include products to ... balloons are the company,s first entry devices for lower ...
Breaking Medicine Technology: