Navigation Links
DNA Repair Proteins Monitored at Double-strand Break

Investigators at St. Jude Children's Research Hospital had a molecules eye view of the human cells DNA repair kit as it assembled on a double-strand break to link together the broken ends. Double-strand breaks are ruptures that cut completely across the twisted, ladder-like structure of DNA, breaking it into two pieces.

Using a technique developed specifically for this project, the St. Jude researchers could determine when repair proteins arrived at or around the DNA break and evaluate its repaireven when particular proteins shifted away from the break to make room for others. A report on this work appears in the May 7 online issue of "Nature Cell Biology."

The findings are important because disruption of the precise movement of these repair proteins can cause mutations, cell death or cancer, and the ability to track the process so closely will give researchers critical insights into what can go wrong with DNA repair. This could lead to novel ways to make cancer cells more sensitive to therapy by blocking their ability to repair double-stranded breaks caused by chemotherapy or radiation. It could also suggest new strategies for enhancing repair of double-stranded DNA caused by radiation, natural oxidants in food or the body and other toxins that can cause disease and aging.

"Prior to this work, there was no practical and efficient way to find and study the DNA repair proteins that organize themselves on and around a double-strand break in human cells," said Michael Kastan, M.D., Ph.D., St. Jude Cancer Center director. "Our approach solved that problem and allowed us to document the cells response to double-strand DNA breaks over time. The technique provides significantly more information about the proteins that repair DNA than is possible using the standard microscope-based approach previously used for such work." Kastan is the papers senior author.

A deficiency in two of these repair proteins, ATM and NBS1, l eads to defects in double-strand break repair by disrupting the signaling processes triggered by the break.

"A lack of functioning ATM causes ataxia-teleangiectasia, a disease that causes a variety of debilitating problems, such as neurodegeneration, cancer and sensitivity to irradiation leading to double-strand breaks that are not repaired," Kastan said.

"And a lack of NBS1 causes Nijmegen breakage syndrome, another disease that leaves its victims at high risk for cancer and higher sensitivity to DNA-damaging radiation. So this work has important medical implications for these and other diseases linked to disruption of double-strand break repair."

The assay, developed by Elijahu Berkovich, Ph.D., in Kastans laboratory, demonstrates how key repair proteins, such as ATM, NBS1, XRCC4 and gamma-H2AX, interact to coordinate repair of double-strand breaks. For example, the investigators showed that NBS1 recruits ATM to the break; and that ATM and NBS1 cooperate to disrupt nucleosomesthe compact packages formed when strands of DNA wind around proteins, called histones, like thread around a spool.

Disruption of the nucleosome at the site of a double-strand break allows the DNA to unravel and expose the area to repair proteins; the loss of functioning ATM and NBS1 blocks this important process. The team also showed that both NBS1 and ATM are needed to ensure that the repair factor, XRCC4, arrives at the double-strand break to help repair the damage.


'"/>




Related medicine news :

1. Brain Cell Repair Loss disclosed
2. Stem Cells To Repair Heart Damage
3. Predictors Of Wound Infection In Ventral Hernia Repair
4. Stem Cells From Hair Follicle To Repair Nerve Damage
5. Little Known DNA Repair Enzyme May Be A Tumor Suppressor Gene
6. Muscle Derived Stem Cell Can Repair Damaged Cartilage
7. Unchecked Cellular Repair Pathway Causes Liver Cancer
8. Bone Marrow Cells Aid In Heart Repair
9. Heart Attack Damage Repaired with Stem cells
10. Pig Stem Cells Show Promise in Repairing Animals’ Heart Attack Damag
11. Stem Cells In Brain Have Potential For Sensing Damage And To Repair
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:10/13/2017)... ... , ... Ellevate Network, the leading network for professional women, brought together some ... at their inaugural Summit in New York City in June. The event was livestreamed ... over 3 million. To watch the Mobilize Women video, click here . ...
(Date:10/13/2017)... ... October 13, 2017 , ... Coveros, ... Development, has been awarded a contract by the Center for Medicare and Medicaid ... to accelerate the enterprise use of Agile methodologies in a consistent and high ...
(Date:10/12/2017)... ... 12, 2017 , ... CitiDent and San Francisco dentists, Dr. ... Oventus O2Vent technology. As many as 18 million Americans are estimated to suffer ... Oral appliances can offer significant relief to about 75 percent of people with ...
(Date:10/12/2017)... ... 12, 2017 , ... The American College of Medical Informatics (ACMI) will present ... the Opening Session of AMIA’s Annual Symposium in Washington, D.C. AMIA’s Annual Symposium ... Collen, a pioneer in the field of medical informatics, this prestigious award is presented ...
(Date:10/12/2017)... ... October 12, 2017 , ... HMP , a leader in ... 2017 Folio Magazine Eddie Digital Award for ‘Best B-to-B Healthcare Website.’ Winners were announced ... 2017. , The annual award competition recognizes editorial and design excellence across a range ...
Breaking Medicine News(10 mins):
(Date:10/2/2017)... ORLANDO, Fla. , Oct. 2, 2017  AllianceRx ... services company formed by Walgreens and pharmacy benefit manager ... of its new brand, which included the unveiling of ... Fla. , as well as at a few ... introduces the new brand to patients, some of whom ...
(Date:9/28/2017)... WASHINGTON , Sept. 28, 2017 Cohen ... to advance the use of wearable and home sensors ... brain disorders. Early Signal Foundation, a nonprofit organization focused ... populations, will provide an affordable analytical system to record ... ...
(Date:9/25/2017)... R.I. , Sept. 25, 2017  EpiVax, ... assessment, vaccine design, and immune-engineering today announced the ... on the development of personalized therapeutic cancer vaccines. ... has provided exclusive access to enabling technologies to ... Eng., MBA will lead EpiVax Oncology as Chief ...
Breaking Medicine Technology: