Radiation Oncology

Findings on DNA Damage Repair Published By UAMS Cancer Researcher

A UAMS research team led by Justin Leung, Ph.D., (pictured front) was published in the journal Nature Communications. Co-authors of the study are Jessica Kelliher, B.S., (left) and Kirk West, Ph.D.

Findings on DNA Damage Repair Published by UAMS Cancer Researcher

By Susan Van Dusen

June 3, 2020 | LITTLE ROCK — A research team led by cancer researcher Justin Leung, Ph.D., at the University of Arkansas for Medical Sciences (UAMS) has uncovered the role of the protein RNF168 in DNA damage repair and shown how mutations of the protein affect people with a rare genetic condition.

The study titled “Histone H2A variants alpha1-extension helix directs RNF168-mediated ubiquitination” was published in the May 18 issue of the open-access journal Nature Communications.

“Every day our cells are subjected to environmental sources of DNA damage, such as ultraviolet radiation and toxic chemical exposure. If left unrepaired, these damages can accumulate, leaving mutations in our DNA and ultimately cause cells to become cancerous,” said Leung, assistant professor in the UAMS College of Medicine Department of Radiation Oncology.

In most cases, this damage is detected and repaired by a tightly regulated method involving many proteins. To develop better cancer therapies, researchers such as Leung strive to understand the regulation of DNA damage and repair by sensitizing cells to radiation therapy and chemotherapy drugs that target DNA.

“Our lab studies the repair of double stranded breaks, where both strands of DNA are broken apart completely. When a double strand break occurs, a cascade of protein activity is set off to try to resolve the damage,” Leung said.

Mutations in one of these proteins, RNF168, have been found in patients with RIDDLE syndrome, a rare genetic disorder that increases a person’s predisposition to blood cancer and is characterized by several attributes:

Susceptibility to DNA damaging agents
Immunodeficiency, or failure of the immune system to protect the body from infection
Developmental abnormalities
Learning disabilities

RNF168 adds a small signaling molecule called ubiquitin onto a subunit of chromatin, where we store our genetic information. The ubiquitin signal brings repair proteins to DNA double strand breaks. However, exactly how RNF168 recognizes the specific target remains unclear.

Using molecular and structural analysis methods, Leung’s team uncovered crucial components of RNF168 and chromatin required for the implementation of repair pathways in response to DNA damage. Their findings suggest that a recognition between RNF168 and chromatin is required to activate the downstream DNA repair processes.

“RNF168 is a central DNA damage response protein. Understanding the precise mechanisms by which it activates its targets is essential for understanding how the DNA damage response goes awry. Our results help demystify the role of RNF168 in proper DNA damage repair and understand the implications of RNF168 mutations such as those seen in RIDDLE syndrome,” Leung said.

UAMS authors for this study included Jessica Kelliher, B.S., research assistant, and Kirk West, Ph.D., postdoctoral fellow.

UAMS is the state's only health sciences university, with colleges of Medicine, Nursing, Pharmacy, Health Professions and Public Health; a graduate school; a hospital; a main campus in Little Rock; a Northwest Arkansas regional campus in Fayetteville; a statewide network of regional campuses; and seven institutes: the Winthrop P. Rockefeller Cancer Institute, Jackson T. Stephens Spine & Neurosciences Institute, Harvey & Bernice Jones Eye Institute, Psychiatric Research Institute, Donald W. Reynolds Institute on Aging, Translational Research Institute and Institute for Digital Health & Innovation. UAMS includes UAMS Health, a statewide health system that encompasses all of UAMS' clinical enterprise. UAMS is the only adult Level 1 trauma center in the state. UAMS has 3,240 students, 913 medical residents and fellows, and five dental residents. It is the state's largest public employer with more than 11,000 employees, including 1,200 physicians who provide care to patients at UAMS, its regional campuses, Arkansas Children's, the VA Medical Center and Baptist Health. Visit www.uams.edu or uamshealth.com. Find us on Facebook, Twitter, YouTube or Instagram.

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UAMS Treats Pediatric Cancer Survivors to a Day at the Zoo

Sept. 14, 2017 | Five-year-old Lilly Johnson may dream of going to Madagascar, but on a recent sunny Saturday she was happy to enjoy some wild animals a little closer to home.

As a patient of the UAMS Radiation Oncology Center (ROC), Lilly and her family were invited to enjoy a day at the Little Rock Zoo for the center’s ROC Star Kids event. The sixth annual gathering held Sept. 9 brought together childhood cancer survivors and their families from across the state. The UAMS Radiation Oncology Center is the only facility in Arkansas that provides radiation therapy for children.

Lilly’s parents, John Paul and Jennifer Johnson, drove their five children two hours from the south Arkansas town of Hermitage to participate. “Lilly dreams of going to Madagascar or Australia just to see the animals, so this was the perfect place for us to come and enjoy the day together,” said Jennifer. It also was perfect timing for Lilly, a Ewing sarcoma survivor, who had both celebrated her birthday and was declared to be in remission within the past two weeks. Ewing sarcoma is a tumor that forms in the bone or soft tissue and most often occurs in children and young adults.

“When a child is diagnosed with cancer, it affects the entire family. We are happy to provide this event each year for these special families to make memories and enjoy some relaxation together,” said Peter Emanuel, M.D., director of the UAMS Winthrop P. Rockefeller Cancer Institute and professor in the UAMS College of Medicine.

A total of 82 pediatric cancer survivors and family members joined in the fun, which included unlimited time viewing the animals; train and carousel rides; and lunch. The event is hosted by the Winthrop P. Rockefeller Cancer Institute Auxiliary.

For the parents, however, these events are more than just a fun family outing.

“Coming to ROC Star Kids reminds us we’re not alone. We share a camaraderie with the other families that helps us keep things in perspective,” said Steve Chamness, whose son, Zach, was diagnosed with medulloblastoma shortly before his second birthday. Although considered a rare cancer, medulloblastoma is the most commonly diagnosed malignant brain tumor in children.

Upon his diagnosis, Zach’s cancer had already spread to his spine and required both regular and high-dose chemotherapy with stem cell transplants at Arkansas Children’s Hospital, in addition to one month of radiation treatments at the UAMS Radiation Oncology Center.

Now 5, Zach is cancer free and attending kindergarten in his hometown of Cabot. “We’re just so grateful,” said his mom, Jill Chamness.

Jamie Weaver echoed that gratefulness about her daughter, Kaylee, and the care she received at UAMS. Diagnosed with neuroblastoma at age 3, Kaylee underwent 10 rounds of radiation therapy at ROC during her 15 total months of treatment. Now in second grade, Kaylee plays soccer, attends Sunday school and is “doing great,” her mom said, adding that she received clear scans earlier that week.

Prior ROC Star Kids events have been held at the UAMS Cancer Institute, an Arkansas Razorbacks football game, Little Rock’s Museum of Discovery and Dickey-Stephens Park. This is the first year to host the event at the Little Rock Zoo.

The program began with the encouragement and support of Arkansas’ former First Lady Ginger Beebe. Beebe’s granddaughter, Alexandria, was diagnosed at 11 weeks old with a tumor encircling her spinal column and was treated successfully at Arkansas Children’s Hospital.

ROC Star Event Hits Homerun for Pediatric Cancer Survivors

Aug. 30, 2016 | For many people, a night at the ballpark is an ordinary summer outing. But for young people with cancer, a simple ballgame can become a lifelong memory.

Creating those memories is the idea behind the ROC Star program, an annual event honoring the children and teens treated at the UAMS Radiation Oncology Center (ROC), the only facility in Arkansas offering radiation therapy for children.

The fifth annual event, hosted by the UAMS Winthrop P. Rockefeller Cancer Institute Auxiliary, was held Aug. 27 at Dickey-Stephens Park in North Little Rock. Guests enjoyed an Arkansas Travelers baseball game and buffet dinner. Prior to the game, the young survivors were introduced to the players and escorted onto the field for the national anthem.

“When a child has cancer, the whole family feels the effects of stress and uncertainty. This event is a chance for them to relax and enjoy a fun evening together,” said Peter Emanuel, M.D., director of the UAMS Cancer Institute.

Twelve-year-old Ewing sarcoma survivor Scout Rodgers and her family were back for their second ROC Star event. “We had a great time last year,” said Scout’s mom, April Rodgers. “Being part of this event really made her feel special.” Ewing sarcoma is a tumor that forms in the bone or soft

tissue and most often occurs in children and young adults.

The youngest of five siblings, 3-year-old Lily Johnson also is undergoing radiation therapy for Ewing sarcoma. “It took a while to figure out what was wrong with Lily, but she just adapts and always has the best attitude,” said mom Jennifer Johnson.

Fellow parent Gina Dickey was happy for her family to make the three-hour drive from Huntsville so daughter Claire could participate. After experiencing a series of headaches in 2014, Claire was diagnosed with a brain tumor at age 3. She underwent more than 30 radiation therapy treatments at ROC.

“When Claire was diagnosed, we were told she might have serious, long-term complications. Thankfully, that never happened. She’s doing well now and just started kindergarten. We’re so happy to be where we are today,” Dickey said.

Prior ROC Star events have been held at the UAMS Cancer Institute, an Arkansas Razorbacks football game and Little Rock’s Museum of Discovery. This was the second year to host the event at Dickey-Stephens Park.