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:6/26/2016)... ... , ... Brent Kasmer, a legally blind and certified personal trainer is helping to develop a ... fitness app plans to fix the two major problems leading the fitness industry today:, ... type program , They don’t eliminate all the reasons people quit their exercise ...
(Date:6/25/2016)... ... ... The temporary closing of Bruton Memorial Library on June 21 due to a possible lice ... overlooked aspect of head lice: the parasite’s ability to live away from a human host, ... a necessary one in the event that lice have simply gotten out of control. , ...
(Date:6/25/2016)... ... June 25, 2016 , ... Dr. Calvin Johnson has ... he has implemented orthobiologic procedures as a method for treating his patients. The ... first doctors to perform the treatment. Orthobiologics are substances that orthopaedic surgeons use ...
(Date:6/24/2016)... ... ... Those who have experienced traumatic events may suffer from a complex set ... drug or alcohol abuse, as a coping mechanism. To avoid this pain and suffering, ... traumatic event. , Trauma sufferers tend to feel a range of emotions, from depression, ...
(Date:6/24/2016)... ... June 24, 2016 , ... Global law firm Greenberg Traurig, P.A. announced that ... chosen by their peers for this recognition are considered among the top 2 percent ... special honors as members of this year’s Legal Elite Hall of Fame: Miami ...
Breaking Medicine News(10 mins):
(Date:6/23/2016)... and INDIANAPOLIS , June ... receiving a Lilly Diabetes Tomorrow,s Leaders Scholarship is any ... scholarship winners, announced today online at www.diabetesscholars.org ... type 1 diabetes stand in the way of academic ... supported the Foundation,s scholarship program since 2012, and continues ...
(Date:6/23/2016)... , June 23, 2016 Revolutionary ... Oticon , industry leaders in advanced audiology ... of Oticon Opn ™, the world,s first internet ... possibilities for IoT devices.      (Photo: ... introduces a number of ,world firsts,: , ...
(Date:6/23/2016)... , June 23, 2016 The vast majority ... outpatient dialysis facility.  Treatments are usually 3 times a ... per visit, including travel time, equipment preparation and wait ... but especially grueling for patients who are elderly and ... skilled nursing and rehabilitation centers for some duration of ...
Breaking Medicine Technology: